Re: Insulin related?

Aaaaah the lord made an obsessive-compulsive (http://www.ocfoundation.org/)
little man!

--
Ken

"Buddhism elucidates why we are sentient."
"Karma means that you don't get away with anything."

"Andrew B. Chung, MD/PhD" <[email hidden]> wrote in message
news:[email hidden]...
| kumar wrote:
|
| For those who are put off by the signature, my advance apologies for
| how the LORD has reshaped me:
|

Quoted message said:

kumar said:

Andrew B. Chung said:

kumar wrote:
> Andrew B. Chung, MD/PhD wrote:
> > kumar wrote:
> > > Andrew B. Chung, MD/PhD wrote:
> > > > kumar wrote:
> > > > > I have following quastions:-
> > > > >
> > > > > 1. Whether enogenous molecules can polymerize in dimers, tetramers,
> > > > > hexamers etc. alfter secretion? If yes, what can be their implications
> > > > > on diabetic patients?
> > > >
> > > > It is not a recognized problem clinically.
> > >
> > > It looks bit odd that long acting exogenous insulin can persist for
> > > long but endogenous not.
> >
> > The exogenous long-acting insulin resides in a different body
> > compartment (subcutaneous).
>
> What will happen when long acting insulin is given intravenously?

It becomes short acting.

Ok, but can diffused/filtered insulin in other compartments can
polymerize and become long acting?

Exogenous "long-acting" formulations can exist in the subcutaneous
compartment in the non-physiological form.

Quoted message said:

Quoted message said:

> I think insulin in polymeric condition is preserved in low pH or with
> zinc. Higher body pH said to monomerize it. Do slow monomerization or
> long acting is due to lesser blood suply in subcutaneous tissues?

There is no comparing the subcutaneous body compartment with the
vascular body compartment.

> What
> is the normal pH of subcutaneous tissues?

Neutral pH around 7.4

How then long acting insulin become short acting in blood but persist
for long in subcutaneous tissues?

Because of inadequate buffering in the subcutaneous environment, the
local pH at the injection site will follow the pH of the injection
solution.

I think then, there can be differenciating effects of injecting insulin
daily due to variations in injecting sites.

How quick acting insulin injected subcutaneous either individually or
mixed with long acting affect quickly? Can it move fast due to its
monomolecular size?

Quoted message said:

Quoted message said:

Quoted message said:

> > > > > 2. Whether exogenous long acting insulin remain in polymer form for
> > > > > long after injecting it? Can it also remain in polymer state for
> > > > > prolonged time(more than as indicated)?
> > > >
> > > > The exact pharmacokinetics will vary from person to person.
> > >
> > > What causes variations in pharmacokinetics of insulin from person to
> > > person?
> >
> > One factor is the amount of subcutaneous body fat.
>
> How amount of subcutaneous body fat causes variations in
> pharmacokinetics of insulin from person to person?

More body fat means slower release of insulin into the bloodstream.

> Is it due to as I
> mentioned as above?

No.

Then how it happens;More body fat means slower release of insulin into
the bloodstream?

More body fat increases the distance from the injection site to the
vascular compartment.

Quoted message said:

Quoted message said:

> > > > > 3. Whether some insulin is not utilized for glucose intake by target
> > > > > cells due to insulin resistance or otherwise? If yes, does it wasted or
> > > > > utilized for other purposes?
> > > >
> > > > The purpose of insulin is to act on target organs as a hormone.
> > >
> > > Yes, but whether all insulin is utilized or not?
> >
> > Hormones are not substrates but rather they are signalling molecules.
> >
> How insulin can perform other actions than causes glucose into the
> cells without its excessive/additional presence?

Insulin is a signalling molecule that interacts with its receptor,
activating it to phosphorylate other proteins at tyrosines to start a
cascade of post-translation modification leading to enhance glucose
transport into the cell.

Let us say, suppose one million molecules of insulin is reqired to
transport 100 million molecules of glucose into the cells in a healthy
non-diabetic person and as such all molecules of insulin and all
molecules of glucose are metabolized.

The insulin is not metabolized in the process of interacting with its
receptors.

What will be the fate of such insulin not metabolized in the process of
interacting with its
receptors.?
?

Quoted message said:

Quoted message said:

What will be the appx. ratio in
diabetic type2 with insulin resistance patient and whether all
molecules of insulin will be metabolized in latter types?

See above.

Quoted message said:

Quoted message said:

> How it it diverted to
> perform other actions without causing hypoglycemia?

Insulin serves to signal need for glucose uptake at target organs.

Do you want to tell that defficiency of insulin either real or due to
its ineffectiveness avtivate body's signals to perform other actions as
indicated in link I first provided? In other sense, insulin is not
directly required to perform other actions as indicated in link than
pursuing glucose entry into cells but its defficiency just trigger
other actions. ??

It is the interaction with its receptor that brings about its effects
and this interaction is reversible because it does not lead to the
catabolism of the insulin. This interaction is concentration-dependent
defined by a binding constant.

Cells changes regularily,. New cells should be having all receptors
intact as insulin resistance is not genetically predisposed. Will then
insulin be normally effective to these new cells?

Quoted message said:

Quoted message said:

Quoted message said:

> > > > > 4. Whether excess insulin, if present due to excess secretion or
> > > > > stimulated by medicines or injected, will cause above indicated actions
> > > > > in excess or not in insulin resistant patients? It looks if in excess
> > > > > those can be quite harmful?
> > > >
> > > > Excessive insulin can result in hypoglycemic shock.
> > >
> > > Sorry but there are many other actions of insulin.
> >
> > Only when physiological and not excessive.
>
> To perform other functions than to cause glucose into the cells, extra
> insulin is needed to be available.

No.

> How such extra insulin stop acting
> for its gulocose related actions and start performing other actions
> without causing hypoglycemia shocks?

The effects are a function of insulin concentration and not absolute
number of insulin molecules.

> > > Whether hypoglycemic
> > > shock is pre other actions or after all possible actions of available
> > > insulin?
> >
> > Excessive amounts of insulin will kill before doing anything else.
>
> Instead of this, can't it be polymerize due to its
> concentration(concentration is a reason for its polymerization),
> degrade/denature or become otherwise in-efective esp. in diabetic T2
> people?

Not in the bloodstream at physiological concentrations.

Can/does insulin polymerize at other comprtments than blood? Can
insulin reverse back from blood into fat tissues polymerize and remain
there for longer period ? In short does our body has any mechanism by
which insulin can be stored and persit for longer time?

Quoted message said:

Quoted message said:

Quoted message said:

>
> > > > > 5. How a insulin resistant patient can get hypoglycemic effect--in view
> > > > > f insulin is not working?
> > > >
> > > > Insulin remains a functional molecule even in insulin resistant
> > > > diabetics.
> > >
> > > Yes but may not completely/efficiently, Can't there be excess insulin
> > > without hypoglycemic shocks due to some disorder?
> >
> > If there is no hypoglycemia, the amount of insulin is not excessive.
>
> Whether normal range of insulin in blood of T2 people can be different
> than non-diabetic people?

It can be somewhat more.

What such more insulin can cause, how it will signal other actions?

Through its receptors which when activated phosphorylates specific
intracellular proteins involved in increasing glucose uptake and
growth.

It looks all actions of insulin is primarily glucose related. Ok?

Thanks you know much more. May be due to both spritual and scientific.
God bless

Kumar said:

Quoted message said:

kumar said:

Andrew B. Chung, MD/PhD wrote:
> kumar wrote:
> > Andrew B. Chung, MD/PhD wrote:
> > > kumar wrote:
> > > > Andrew B. Chung, MD/PhD wrote:
> > > > > kumar wrote:
> > > > > > I have following quastions:-
> > > > > >
> > > > > > 1. Whether enogenous molecules can polymerize in dimers, tetramers,
> > > > > > hexamers etc. alfter secretion? If yes, what can be their implications
> > > > > > on diabetic patients?
> > > > >
> > > > > It is not a recognized problem clinically.
> > > >
> > > > It looks bit odd that long acting exogenous insulin can persist for
> > > > long but endogenous not.
> > >
> > > The exogenous long-acting insulin resides in a different body
> > > compartment (subcutaneous).
> >
> > What will happen when long acting insulin is given intravenously?
>
> It becomes short acting.
>
Ok, but can diffused/filtered insulin in other compartments can
polymerize and become long acting?

Exogenous "long-acting" formulations can exist in the subcutaneous
compartment in the non-physiological form.

Quoted message said:

> > I think insulin in polymeric condition is preserved in low pH or with
> > zinc. Higher body pH said to monomerize it. Do slow monomerization or
> > long acting is due to lesser blood suply in subcutaneous tissues?
>
> There is no comparing the subcutaneous body compartment with the
> vascular body compartment.
>
> > What
> > is the normal pH of subcutaneous tissues?
>
> Neutral pH around 7.4
>
How then long acting insulin become short acting in blood but persist
for long in subcutaneous tissues?

Because of inadequate buffering in the subcutaneous environment, the
local pH at the injection site will follow the pH of the injection
solution.

I think then, there can be differenciating effects of injecting insulin
daily due to variations in injecting sites.

In practice, we don't see it probably because the amount of food that
people eat varies widely.

Quoted message said:

How quick acting insulin injected subcutaneous either individually or
mixed with long acting affect quickly? Can it move fast due to its
monomolecular size?

Yes.

Quoted message said:

Quoted message said:

Quoted message said:

> > > > > > 2. Whether exogenous long acting insulin remain in polymer form for
> > > > > > long after injecting it? Can it also remain in polymer state for
> > > > > > prolonged time(more than as indicated)?
> > > > >
> > > > > The exact pharmacokinetics will vary from person to person.
> > > >
> > > > What causes variations in pharmacokinetics of insulin from person to
> > > > person?
> > >
> > > One factor is the amount of subcutaneous body fat.
> >
> > How amount of subcutaneous body fat causes variations in
> > pharmacokinetics of insulin from person to person?
>
> More body fat means slower release of insulin into the bloodstream.
>
> > Is it due to as I
> > mentioned as above?
>
> No.
>
Then how it happens;More body fat means slower release of insulin into
the bloodstream?

More body fat increases the distance from the injection site to the
vascular compartment.

Quoted message said:

> > > > > > 3. Whether some insulin is not utilized for glucose intake by target
> > > > > > cells due to insulin resistance or otherwise? If yes, does it wasted or
> > > > > > utilized for other purposes?
> > > > >
> > > > > The purpose of insulin is to act on target organs as a hormone.
> > > >
> > > > Yes, but whether all insulin is utilized or not?
> > >
> > > Hormones are not substrates but rather they are signalling molecules.
> > >
> > How insulin can perform other actions than causes glucose into the
> > cells without its excessive/additional presence?
>
> Insulin is a signalling molecule that interacts with its receptor,
> activating it to phosphorylate other proteins at tyrosines to start a
> cascade of post-translation modification leading to enhance glucose
> transport into the cell.
>
Let us say, suppose one million molecules of insulin is reqired to
transport 100 million molecules of glucose into the cells in a healthy
non-diabetic person and as such all molecules of insulin and all
molecules of glucose are metabolized.

The insulin is not metabolized in the process of interacting with its
receptors.

What will be the fate of such insulin not metabolized in the process of
interacting with its
receptors.?

It has additional opportunities for intermolecular interactions.

Quoted message said:

Quoted message said:

Quoted message said:

What will be the appx. ratio in
diabetic type2 with insulin resistance patient and whether all
molecules of insulin will be metabolized in latter types?

See above.

Quoted message said:

> > How it it diverted to
> > perform other actions without causing hypoglycemia?
>
> Insulin serves to signal need for glucose uptake at target organs.
>
Do you want to tell that defficiency of insulin either real or due to
its ineffectiveness avtivate body's signals to perform other actions as
indicated in link I first provided? In other sense, insulin is not
directly required to perform other actions as indicated in link than
pursuing glucose entry into cells but its defficiency just trigger
other actions. ??

It is the interaction with its receptor that brings about its effects
and this interaction is reversible because it does not lead to the
catabolism of the insulin. This interaction is concentration-dependent
defined by a binding constant.

Cells changes regularily,.

The receptors don't,

Quoted message said:

New cells should be having all receptors
intact as insulin resistance is not genetically predisposed.

Actually, there is a genetic predisposition toward developing insulin
resistance.

Quoted message said:

Will then
insulin be normally effective to these new cells?

Not in the setting of metabolic syndrome (MetS).

Quoted message said:

Quoted message said:

Quoted message said:

> > > > > > 4. Whether excess insulin, if present due to excess secretion or
> > > > > > stimulated by medicines or injected, will cause above indicated actions
> > > > > > in excess or not in insulin resistant patients? It looks if in excess
> > > > > > those can be quite harmful?
> > > > >
> > > > > Excessive insulin can result in hypoglycemic shock.
> > > >
> > > > Sorry but there are many other actions of insulin.
> > >
> > > Only when physiological and not excessive.
> >
> > To perform other functions than to cause glucose into the cells, extra
> > insulin is needed to be available.
>
> No.
>
> > How such extra insulin stop acting
> > for its gulocose related actions and start performing other actions
> > without causing hypoglycemia shocks?
>
> The effects are a function of insulin concentration and not absolute
> number of insulin molecules.
>
> > > > Whether hypoglycemic
> > > > shock is pre other actions or after all possible actions of available
> > > > insulin?
> > >
> > > Excessive amounts of insulin will kill before doing anything else.
> >
> > Instead of this, can't it be polymerize due to its
> > concentration(concentration is a reason for its polymerization),
> > degrade/denature or become otherwise in-efective esp. in diabetic T2
> > people?
>
> Not in the bloodstream at physiological concentrations.

Can/does insulin polymerize at other comprtments than blood?

Hydrostatic and electrostatic interactions do not involve the formation
of covalent bonds necessary for polymerization.

Quoted message said:

Can
insulin reverse back from blood into fat tissues polymerize and remain
there for longer period ?

No.

Quoted message said:

In short does our body has any mechanism by
which insulin can be stored and persit for longer time?

No. If it did, insulin would lose its ability to signal.

Quoted message said:

Quoted message said:

Quoted message said:

>
> >
> > > > > > 5. How a insulin resistant patient can get hypoglycemic effect--in view
> > > > > > f insulin is not working?
> > > > >
> > > > > Insulin remains a functional molecule even in insulin resistant
> > > > > diabetics.
> > > >
> > > > Yes but may not completely/efficiently, Can't there be excess insulin
> > > > without hypoglycemic shocks due to some disorder?
> > >
> > > If there is no hypoglycemia, the amount of insulin is not excessive.
> >
> > Whether normal range of insulin in blood of T2 people can be different
> > than non-diabetic people?
>
> It can be somewhat more.

What such more insulin can cause, how it will signal other actions?

Through its receptors which when activated phosphorylates specific
intracellular proteins involved in increasing glucose uptake and
growth.

It looks all actions of insulin is primarily glucose related. Ok?

It also promotes growth.

Quoted message said:

Thanks you know much more. May be due to both spritual and scientific.

It is all due to the LORD, Whom I love with all my being :-))

Quoted message said:

God bless

Thank you for your kind thoughts.

Will be available to "glow" and chat about this and other things like
cardiology, diabetes, cooking and nutrition that interest those
following this thread here during the next on-line chat (02/02/06) from
6 to 7 pm EST:

http://tinyurl.com/cpayh

For those who are put off by the signature, my advance apologies for
how the LORD has reshaped me:

http://tinyurl.com/bgfqt

Prayerfully in Christ's love,

Andrew
http://tinyurl.com/8juld

Andrew B. Chung said:

Kumar said:

Quoted message said:

kumar wrote:
> Andrew B. Chung, MD/PhD wrote:
> > kumar wrote:
> > > Andrew B. Chung, MD/PhD wrote:
> > > > kumar wrote:
> > > > > Andrew B. Chung, MD/PhD wrote:
> > > > > > kumar wrote:
> > > > > > > I have following quastions:-
> > > > > > >
> > > > > > > 1. Whether enogenous molecules can polymerize in dimers, tetramers,
> > > > > > > hexamers etc. alfter secretion? If yes, what can be their implications
> > > > > > > on diabetic patients?
> > > > > >
> > > > > > It is not a recognized problem clinically.
> > > > >
> > > > > It looks bit odd that long acting exogenous insulin can persist for
> > > > > long but endogenous not.
> > > >
> > > > The exogenous long-acting insulin resides in a different body
> > > > compartment (subcutaneous).
> > >
> > > What will happen when long acting insulin is given intravenously?
> >
> > It becomes short acting.
> >
> Ok, but can diffused/filtered insulin in other compartments can
> polymerize and become long acting?

Exogenous "long-acting" formulations can exist in the subcutaneous
compartment in the non-physiological form.

> > > I think insulin in polymeric condition is preserved in low pH or with
> > > zinc. Higher body pH said to monomerize it. Do slow monomerization or
> > > long acting is due to lesser blood suply in subcutaneous tissues?
> >
> > There is no comparing the subcutaneous body compartment with the
> > vascular body compartment.
> >
> > > What
> > > is the normal pH of subcutaneous tissues?
> >
> > Neutral pH around 7.4
> >
> How then long acting insulin become short acting in blood but persist
> for long in subcutaneous tissues?

Because of inadequate buffering in the subcutaneous environment, the
local pH at the injection site will follow the pH of the injection
solution.

I think then, there can be differenciating effects of injecting insulin
daily due to variations in injecting sites.

In practice, we don't see it probably because the amount of food that
people eat varies widely.

Previously when syringe with long needle was common for injecting
insulin, insulin was better controlled. Now pen nd short needle is
common. Can there be some variations in effect by injected insulin
(esp. long cting) due to size of needle in view of these discussions?

Quoted message said:

Quoted message said:

How quick acting insulin injected subcutaneous either individually or
mixed with long acting affect quickly? Can it move fast due to its
monomolecular size?

Yes.

Is there any other resistance in transporting injected insulin to
vascular compartment?

Quoted message said:

Quoted message said:

Quoted message said:

> > > > > > > 2. Whether exogenous long acting insulin remain in polymer form for
> > > > > > > long after injecting it? Can it also remain in polymer state for
> > > > > > > prolonged time(more than as indicated)?
> > > > > >
> > > > > > The exact pharmacokinetics will vary from person to person.
> > > > >
> > > > > What causes variations in pharmacokinetics of insulin from person to
> > > > > person?
> > > >
> > > > One factor is the amount of subcutaneous body fat.
> > >
> > > How amount of subcutaneous body fat causes variations in
> > > pharmacokinetics of insulin from person to person?
> >
> > More body fat means slower release of insulin into the bloodstream.
> >
> > > Is it due to as I
> > > mentioned as above?
> >
> > No.
> >
> Then how it happens;More body fat means slower release of insulin into
> the bloodstream?

More body fat increases the distance from the injection site to the
vascular compartment.

> > > > > > > 3. Whether some insulin is not utilized for glucose intake by target
> > > > > > > cells due to insulin resistance or otherwise? If yes, does it wasted or
> > > > > > > utilized for other purposes?
> > > > > >
> > > > > > The purpose of insulin is to act on target organs as a hormone.
> > > > >
> > > > > Yes, but whether all insulin is utilized or not?
> > > >
> > > > Hormones are not substrates but rather they are signalling molecules.
> > > >
> > > How insulin can perform other actions than causes glucose into the
> > > cells without its excessive/additional presence?
> >
> > Insulin is a signalling molecule that interacts with its receptor,
> > activating it to phosphorylate other proteins at tyrosines to start a
> > cascade of post-translation modification leading to enhance glucose
> > transport into the cell.
> >
> Let us say, suppose one million molecules of insulin is reqired to
> transport 100 million molecules of glucose into the cells in a healthy
> non-diabetic person and as such all molecules of insulin and all
> molecules of glucose are metabolized.

The insulin is not metabolized in the process of interacting with its
receptors.

What will be the fate of such insulin not metabolized in the process of
interacting with its
receptors.?

It has additional opportunities for intermolecular interactions.

What are these intermolecular interactions?

Quoted message said:

Quoted message said:

Quoted message said:

> What will be the appx. ratio in
> diabetic type2 with insulin resistance patient and whether all
> molecules of insulin will be metabolized in latter types?

See above.

> > > How it it diverted to
> > > perform other actions without causing hypoglycemia?
> >
> > Insulin serves to signal need for glucose uptake at target organs.
> >
> Do you want to tell that defficiency of insulin either real or due to
> its ineffectiveness avtivate body's signals to perform other actions as
> indicated in link I first provided? In other sense, insulin is not
> directly required to perform other actions as indicated in link than
> pursuing glucose entry into cells but its defficiency just trigger
> other actions. ??

It is the interaction with its receptor that brings about its effects
and this interaction is reversible because it does not lead to the
catabolism of the insulin. This interaction is concentration-dependent
defined by a binding constant.

Cells changes regularily,.

The receptors don't,

Quoted message said:

New cells should be having all receptors
intact as insulin resistance is not genetically predisposed.

Actually, there is a genetic predisposition toward developing insulin
resistance.

How then it is reversible by correcting obesity esp.in diabetics who
have not yet start taking insulin injections?

Quoted message said:

Quoted message said:

Will then
insulin be normally effective to these new cells?

Not in the setting of metabolic syndrome (MetS).

Quoted message said:

Quoted message said:

> > > > > > > 4. Whether excess insulin, if present due to excess secretion or
> > > > > > > stimulated by medicines or injected, will cause above indicated actions
> > > > > > > in excess or not in insulin resistant patients? It looks if in excess
> > > > > > > those can be quite harmful?
> > > > > >
> > > > > > Excessive insulin can result in hypoglycemic shock.
> > > > >
> > > > > Sorry but there are many other actions of insulin.
> > > >
> > > > Only when physiological and not excessive.
> > >
> > > To perform other functions than to cause glucose into the cells, extra
> > > insulin is needed to be available.
> >
> > No.
> >
> > > How such extra insulin stop acting
> > > for its gulocose related actions and start performing other actions
> > > without causing hypoglycemia shocks?
> >
> > The effects are a function of insulin concentration and not absolute
> > number of insulin molecules.
> >
> > > > > Whether hypoglycemic
> > > > > shock is pre other actions or after all possible actions of available
> > > > > insulin?
> > > >
> > > > Excessive amounts of insulin will kill before doing anything else.
> > >
> > > Instead of this, can't it be polymerize due to its
> > > concentration(concentration is a reason for its polymerization),
> > > degrade/denature or become otherwise in-efective esp. in diabetic T2
> > > people?
> >
> > Not in the bloodstream at physiological concentrations.

Can/does insulin polymerize at other comprtments than blood?

Hydrostatic and electrostatic interactions do not involve the formation
of covalent bonds necessary for polymerization.

Sorry but I think, It is intermolecular association attached by
intermolecular forces necessary for polymerization not by covalent
bonding.

Quoted message said:

Quoted message said:

Can
insulin reverse back from blood into fat tissues polymerize and remain
there for longer period ?

No.

Quoted message said:

In short does our body has any mechanism by
which insulin can be stored and persit for longer time?

No. If it did, insulin would lose its ability to signal.

Yes, but on getting diabeteswith IR, it looks alike as insulin is
working lesser.

Quoted message said:

Quoted message said:

Quoted message said:

> >
> > >
> > > > > > > 5. How a insulin resistant patient can get hypoglycemic effect--in view
> > > > > > > f insulin is not working?
> > > > > >
> > > > > > Insulin remains a functional molecule even in insulin resistant
> > > > > > diabetics.
> > > > >
> > > > > Yes but may not completely/efficiently, Can't there be excess insulin
> > > > > without hypoglycemic shocks due to some disorder?
> > > >
> > > > If there is no hypoglycemia, the amount of insulin is not excessive.
> > >
> > > Whether normal range of insulin in blood of T2 people can be different
> > > than non-diabetic people?
> >
> > It can be somewhat more.
>
> What such more insulin can cause, how it will signal other actions?

Through its receptors which when activated phosphorylates specific
intracellular proteins involved in increasing glucose uptake and
growth.

It looks all actions of insulin is primarily glucose related. Ok?

It also promotes growth.

How?

Quoted message said:

Quoted message said:

Thanks you know much more. May be due to both spritual and scientific.

It is all due to the LORD, Whom I love with all my being :-))

Quoted message said:

God bless

Thank you for your kind thoughts.

Kumar said:

Andrew B. Chung said:

Kumar said:

> kumar wrote:
> > Andrew B. Chung, MD/PhD wrote:
> > > kumar wrote:
> > > > Andrew B. Chung, MD/PhD wrote:
> > > > > kumar wrote:
> > > > > > Andrew B. Chung, MD/PhD wrote:
> > > > > > > kumar wrote:
> > > > > > > > I have following quastions:-
> > > > > > > >
> > > > > > > > 1. Whether enogenous molecules can polymerize in dimers, tetramers,
> > > > > > > > hexamers etc. alfter secretion? If yes, what can be their implications
> > > > > > > > on diabetic patients?
> > > > > > >
> > > > > > > It is not a recognized problem clinically.
> > > > > >
> > > > > > It looks bit odd that long acting exogenous insulin can persist for
> > > > > > long but endogenous not.
> > > > >
> > > > > The exogenous long-acting insulin resides in a different body
> > > > > compartment (subcutaneous).
> > > >
> > > > What will happen when long acting insulin is given intravenously?
> > >
> > > It becomes short acting.
> > >
> > Ok, but can diffused/filtered insulin in other compartments can
> > polymerize and become long acting?
>
> Exogenous "long-acting" formulations can exist in the subcutaneous
> compartment in the non-physiological form.
>
> > > > I think insulin in polymeric condition is preserved in low pH or with
> > > > zinc. Higher body pH said to monomerize it. Do slow monomerization or
> > > > long acting is due to lesser blood suply in subcutaneous tissues?
> > >
> > > There is no comparing the subcutaneous body compartment with the
> > > vascular body compartment.
> > >
> > > > What
> > > > is the normal pH of subcutaneous tissues?
> > >
> > > Neutral pH around 7.4
> > >
> > How then long acting insulin become short acting in blood but persist
> > for long in subcutaneous tissues?
>
> Because of inadequate buffering in the subcutaneous environment, the
> local pH at the injection site will follow the pH of the injection
> solution.
>
I think then, there can be differenciating effects of injecting insulin
daily due to variations in injecting sites.

In practice, we don't see it probably because the amount of food that
people eat varies widely.

Previously when syringe with long needle was common for injecting
insulin, insulin was better controlled. Now pen nd short needle is
common. Can there be some variations in effect by injected insulin
(esp. long cting) due to size of needle in view of these discussions?

I have not noticed it.

Quoted message said:

Quoted message said:

Quoted message said:

How quick acting insulin injected subcutaneous either individually or
mixed with long acting affect quickly? Can it move fast due to its
monomolecular size?

Yes.

Is there any other resistance in transporting injected insulin to
vascular compartment?

No.

Quoted message said:

Quoted message said:

Quoted message said:

> > > > > > > > 2. Whether exogenous long acting insulin remain in polymer form for
> > > > > > > > long after injecting it? Can it also remain in polymer state for
> > > > > > > > prolonged time(more than as indicated)?
> > > > > > >
> > > > > > > The exact pharmacokinetics will vary from person to person.
> > > > > >
> > > > > > What causes variations in pharmacokinetics of insulin from person to
> > > > > > person?
> > > > >
> > > > > One factor is the amount of subcutaneous body fat.
> > > >
> > > > How amount of subcutaneous body fat causes variations in
> > > > pharmacokinetics of insulin from person to person?
> > >
> > > More body fat means slower release of insulin into the bloodstream.
> > >
> > > > Is it due to as I
> > > > mentioned as above?
> > >
> > > No.
> > >
> > Then how it happens;More body fat means slower release of insulin into
> > the bloodstream?
>
> More body fat increases the distance from the injection site to the
> vascular compartment.
>
> > > > > > > > 3. Whether some insulin is not utilized for glucose intake by target
> > > > > > > > cells due to insulin resistance or otherwise? If yes, does it wasted or
> > > > > > > > utilized for other purposes?
> > > > > > >
> > > > > > > The purpose of insulin is to act on target organs as a hormone.
> > > > > >
> > > > > > Yes, but whether all insulin is utilized or not?
> > > > >
> > > > > Hormones are not substrates but rather they are signalling molecules.
> > > > >
> > > > How insulin can perform other actions than causes glucose into the
> > > > cells without its excessive/additional presence?
> > >
> > > Insulin is a signalling molecule that interacts with its receptor,
> > > activating it to phosphorylate other proteins at tyrosines to start a
> > > cascade of post-translation modification leading to enhance glucose
> > > transport into the cell.
> > >
> > Let us say, suppose one million molecules of insulin is reqired to
> > transport 100 million molecules of glucose into the cells in a healthy
> > non-diabetic person and as such all molecules of insulin and all
> > molecules of glucose are metabolized.
>
> The insulin is not metabolized in the process of interacting with its
> receptors.
>
What will be the fate of such insulin not metabolized in the process of
interacting with its
receptors.?

It has additional opportunities for intermolecular interactions.

What are these intermolecular interactions?

Receptor binding.

Quoted message said:

Quoted message said:

Quoted message said:

> > What will be the appx. ratio in
> > diabetic type2 with insulin resistance patient and whether all
> > molecules of insulin will be metabolized in latter types?
>
> See above.
>
> > > > How it it diverted to
> > > > perform other actions without causing hypoglycemia?
> > >
> > > Insulin serves to signal need for glucose uptake at target organs.
> > >
> > Do you want to tell that defficiency of insulin either real or due to
> > its ineffectiveness avtivate body's signals to perform other actions as
> > indicated in link I first provided? In other sense, insulin is not
> > directly required to perform other actions as indicated in link than
> > pursuing glucose entry into cells but its defficiency just trigger
> > other actions. ??
>
> It is the interaction with its receptor that brings about its effects
> and this interaction is reversible because it does not lead to the
> catabolism of the insulin. This interaction is concentration-dependent
> defined by a binding constant.
>
Cells changes regularily,.

The receptors don't,

Quoted message said:

New cells should be having all receptors
intact as insulin resistance is not genetically predisposed.

Actually, there is a genetic predisposition toward developing insulin
resistance.

How then it is reversible by correcting obesity esp.in diabetics who
have not yet start taking insulin injections?

By decreasing levels of inflammatory cytokines which are produced by
visceral adipocytes.

Quoted message said:

Quoted message said:

Quoted message said:

Will then
insulin be normally effective to these new cells?

Not in the setting of metabolic syndrome (MetS).

Quoted message said:

> > > > > > > > 4. Whether excess insulin, if present due to excess secretion or
> > > > > > > > stimulated by medicines or injected, will cause above indicated actions
> > > > > > > > in excess or not in insulin resistant patients? It looks if in excess
> > > > > > > > those can be quite harmful?
> > > > > > >
> > > > > > > Excessive insulin can result in hypoglycemic shock.
> > > > > >
> > > > > > Sorry but there are many other actions of insulin.
> > > > >
> > > > > Only when physiological and not excessive.
> > > >
> > > > To perform other functions than to cause glucose into the cells, extra
> > > > insulin is needed to be available.
> > >
> > > No.
> > >
> > > > How such extra insulin stop acting
> > > > for its gulocose related actions and start performing other actions
> > > > without causing hypoglycemia shocks?
> > >
> > > The effects are a function of insulin concentration and not absolute
> > > number of insulin molecules.
> > >
> > > > > > Whether hypoglycemic
> > > > > > shock is pre other actions or after all possible actions of available
> > > > > > insulin?
> > > > >
> > > > > Excessive amounts of insulin will kill before doing anything else.
> > > >
> > > > Instead of this, can't it be polymerize due to its
> > > > concentration(concentration is a reason for its polymerization),
> > > > degrade/denature or become otherwise in-efective esp. in diabetic T2
> > > > people?
> > >
> > > Not in the bloodstream at physiological concentrations.

Can/does insulin polymerize at other comprtments than blood?

Hydrostatic and electrostatic interactions do not involve the formation
of covalent bonds necessary for polymerization.

Sorry but I think, It is intermolecular association attached by
intermolecular forces necessary for polymerization not by covalent
bonding.

The term polymerization, by definition, involves the formation of
covalent bonds.

Quoted message said:

Quoted message said:

Quoted message said:

Can
insulin reverse back from blood into fat tissues polymerize and remain
there for longer period ?

No.

Quoted message said:

In short does our body has any mechanism by
which insulin can be stored and persit for longer time?

No. If it did, insulin would lose its ability to signal.

Yes, but on getting diabeteswith IR, it looks alike as insulin is
working lesser.

It still works as a signal even if less effectively.

Quoted message said:

Quoted message said:

Quoted message said:

> > >
> > > >
> > > > > > > > 5. How a insulin resistant patient can get hypoglycemic effect--in view
> > > > > > > > f insulin is not working?
> > > > > > >
> > > > > > > Insulin remains a functional molecule even in insulin resistant
> > > > > > > diabetics.
> > > > > >
> > > > > > Yes but may not completely/efficiently, Can't there be excess insulin
> > > > > > without hypoglycemic shocks due to some disorder?
> > > > >
> > > > > If there is no hypoglycemia, the amount of insulin is not excessive.
> > > >
> > > > Whether normal range of insulin in blood of T2 people can be different
> > > > than non-diabetic people?
> > >
> > > It can be somewhat more.
> >
> > What such more insulin can cause, how it will signal other actions?
>
> Through its receptors which when activated phosphorylates specific
> intracellular proteins involved in increasing glucose uptake and
> growth.
It looks all actions of insulin is primarily glucose related. Ok?

It also promotes growth.

How?

Through receptor-mediated post-translational modification (tyrosine
phosporylation) of intracellular proteins involved in cellular growth.

Will be available to "glow" and chat about this and other things like
cardiology, diabetes, cooking and nutrition that interest those
following this thread here during the next on-line chat (02/02/06) from
6 to 7 pm EST:

http://tinyurl.com/cpayh

For those who are put off by the signature, my advance apologies for
how the LORD has reshaped me:

http://tinyurl.com/bgfqt

Prayerfully in Christ's love,

Andrew
http://tinyurl.com/8juld

Andrew B. Chung said:

Kumar said:

Is there any other resistance in transporting injected insulin to
vascular compartment?

No.

Can insulin molecules in blood or at other compartment be aggregated or
associated by intermolecular forces without polymerization? If yes, can
this condition exist for long?

Quoted message said:

Quoted message said:

What are these intermolecular interactions?

Receptor binding.

Good thanks.

Quoted message said:

Quoted message said:

Quoted message said:

Actually, there is a genetic predisposition toward developing insulin
resistance.

How then it is reversible by correcting obesity esp.in diabetics who
have not yet start taking insulin injections?

By decreasing levels of inflammatory cytokines which are produced by
visceral adipocytes.

How then there can be a genetic predisposition towards developing
insulin resistance?

Whether inflammatory cytokines which are produced by visceral
adipocytes is only reason to getting IR or all inflammatory responses
can cause insulin resistance and hyperglycemia(infections are already
indicated to increse blood glucose levels)?

As such, can greater adiposity or obesity be treated as inflammatory
diseases?

Quoted message said:

Quoted message said:

Quoted message said:

> Will then
> insulin be normally effective to these new cells?

Not in the setting of metabolic syndrome (MetS).

Does it indicate that it is due to genetic predisposition?

..

Quoted message said:

Quoted message said:

Quoted message said:

> Can/does insulin polymerize at other comprtments than blood?

Hydrostatic and electrostatic interactions do not involve the formation
of covalent bonds necessary for polymerization.

Are there Hydrostatic and electrostatic intermolecular interactions
between insulin molecules which may keep these molecules
associated/aggregated enabling these to escape filteration/loss via
kidneys and stored or act for long time as per need?
..

Quoted message said:

The term polymerization, by definition, involves the formation of
covalent bonds.

Yes, thanks.

Quoted message said:

Quoted message said:

Quoted message said:

> In short does our body has any mechanism by
> which insulin can be stored and persit for longer time?

No. If it did, insulin would lose its ability to signal.

Yes, but on getting diabeteswith IR, it looks alike as insulin is
working lesser.

It still works as a signal even if less effectively.

It works less, whether due to receptor's regulations changes?

Quoted message said:

Quoted message said:

Quoted message said:

> > > What such more insulin can cause, how it will signal other actions?
> >
> > Through its receptors which when activated phosphorylates specific
> > intracellular proteins involved in increasing glucose uptake and
> > growth.
> It looks all actions of insulin is primarily glucose related. Ok?

It also promotes growth.

How?

Through receptor-mediated post-translational modification (tyrosine
phosporylation) of intracellular proteins involved in cellular growth.

Thanks.

Kumar said:

Andrew B. Chung said:

Kumar said:

Is there any other resistance in transporting injected insulin to
vascular compartment?

No.

Can insulin molecules in blood or at other compartment be aggregated or
associated by intermolecular forces without polymerization?

Yes.

Quoted message said:

If yes, can
this condition exist for long?

Perhaps if conditions are non-physiological.

Quoted message said:

Quoted message said:

Quoted message said:

What are these intermolecular interactions?

Receptor binding.

Good thanks.

You are welcome :-)

Quoted message said:

Quoted message said:

Quoted message said:

> Actually, there is a genetic predisposition toward developing insulin
> resistance.
>
How then it is reversible by correcting obesity esp.in diabetics who
have not yet start taking insulin injections?

By decreasing levels of inflammatory cytokines which are produced by
visceral adipocytes.

How then there can be a genetic predisposition towards developing
insulin resistance?

There are a number of possibilities. One example is that it could
occur with the genetic predisposition to develop visceral adiposity.

Quoted message said:

Whether inflammatory cytokines which are produced by visceral
adipocytes is only reason to getting IR or all inflammatory responses
can cause insulin resistance and hyperglycemia(infections are already
indicated to increse blood glucose levels)?

Chronically elevated levels of inflammatory cytokines likely has the
potential for causing IR regardless of the primary cause.

Quoted message said:

As such, can greater adiposity or obesity be treated as inflammatory
diseases?

Far wiser would be to address the primary reason for the
adiposity/obesity.

Quoted message said:

Quoted message said:

Quoted message said:

> > Will then
> > insulin be normally effective to these new cells?
>
> Not in the setting of metabolic syndrome (MetS).

Does it indicate that it is due to genetic predisposition?

There is a genetic predisposition to develop MetS.

Quoted message said:

Quoted message said:

Quoted message said:

> > Can/does insulin polymerize at other comprtments than blood?
>
> Hydrostatic and electrostatic interactions do not involve the formation
> of covalent bonds necessary for polymerization.

Are there Hydrostatic and electrostatic intermolecular interactions
between insulin molecules which may keep these molecules
associated/aggregated enabling these to escape filteration/loss via
kidneys and stored or act for long time as per need?

Probably not under physiological conditions. Again, insulin is
catabolized by the kidneys and not excreted.

Quoted message said:

Quoted message said:

The term polymerization, by definition, involves the formation of
covalent bonds.

Yes, thanks.

Again, you are welcome.

Quoted message said:

Quoted message said:

Quoted message said:

> > In short does our body has any mechanism by
> > which insulin can be stored and persit for longer time?
>
> No. If it did, insulin would lose its ability to signal.
>
Yes, but on getting diabeteswith IR, it looks alike as insulin is
working lesser.

It still works as a signal even if less effectively.

It works less, whether due to receptor's regulations changes?

There is storage of insulin occurring in extracellular compartments.

Quoted message said:

Quoted message said:

Quoted message said:

> > > > What such more insulin can cause, how it will signal other actions?
> > >
> > > Through its receptors which when activated phosphorylates specific
> > > intracellular proteins involved in increasing glucose uptake and
> > > growth.
> > It looks all actions of insulin is primarily glucose related. Ok?
>
> It also promotes growth.
>
How?

Through receptor-mediated post-translational modification (tyrosine
phosporylation) of intracellular proteins involved in cellular growth.

Thanks.

You are welcome :-)

All thanks and praises belong to the LORD, Whom I love with all my
heart, soul, mind, and strength :-))

Will be available to "glow" and chat about this and other things like
cardiology, diabetes, cooking and nutrition that interest those
following this thread here during the next on-line chat (02/02/06) from
6 to 7 pm EST:

http://tinyurl.com/cpayh

For those who are put off by the signature, my advance apologies for
how the LORD has reshaped me:

http://tinyurl.com/bgfqt

Prayerfully in Christ's love,

Andrew
http://tinyurl.com/8juld

Andrew B. Chung said:

Kumar said:

Andrew B. Chung said:

Kumar wrote:
> Is there any other resistance in transporting injected insulin to
> vascular compartment?

No.

Can insulin molecules in blood or at other compartment be aggregated or
associated by intermolecular forces without polymerization?

Yes.

Can you tell some more detail about it? What is medical condition named
for it?

Quoted message said:

Quoted message said:

If yes, can
this condition exist for long?

Perhaps if conditions are non-physiological.

Quoted message said:

Quoted message said:

> What are these intermolecular interactions?

Receptor binding.

Good thanks.

You are welcome :-)

Quoted message said:

Quoted message said:

> > Actually, there is a genetic predisposition toward developing insulin
> > resistance.
> >
> How then it is reversible by correcting obesity esp.in diabetics who
> have not yet start taking insulin injections?

By decreasing levels of inflammatory cytokines which are produced by
visceral adipocytes.

How then there can be a genetic predisposition towards developing
insulin resistance?

There are a number of possibilities. One example is that it could
occur with the genetic predisposition to develop visceral adiposity.

To get fat depositions or visceral adiposity, whether digestive acidic
or alkaline secretions and balanced insulin secretions is needed to be
changed/imbalanced?

Can low gastric acid, excess bile and low bicarbonate cause excess
intestinal fats digestion and absorption?

Quoted message said:

Quoted message said:

Whether inflammatory cytokines which are produced by visceral
adipocytes is only reason to getting IR or all inflammatory responses
can cause insulin resistance and hyperglycemia(infections are already
indicated to increse blood glucose levels)?

Chronically elevated levels of inflammatory cytokines likely has the
potential for causing IR regardless of the primary cause.

Whether Chronically elevated levels of inflammatory cytokines can be
the only/main cause of getting IR?

Quoted message said:

Quoted message said:

As such, can greater adiposity or obesity be treated as inflammatory
diseases?

Far wiser would be to address the primary reason for the
adiposity/obesity.

What is that? Is it taking excess glucose/fats?

Quoted message said:

Quoted message said:

Quoted message said:

> > > Will then
> > > insulin be normally effective to these new cells?
> >
> > Not in the setting of metabolic syndrome (MetS).

Does it indicate that it is due to genetic predisposition?

There is a genetic predisposition to develop MetS.

Can genetic predisostions in diabetes2 basically cause excess cravings
to foods resulting into more food intake>>more glucose>>more
insulin>>IR>>hyperglycemia....?

If yes, how this excess craving is oriented? Is it by genetic
predisposition to get excess gastric acid and insulin secretion?

Quoted message said:

Quoted message said:

Quoted message said:

> > > Can/does insulin polymerize at other comprtments than blood?
> >
> > Hydrostatic and electrostatic interactions do not involve the formation
> > of covalent bonds necessary for polymerization.

Are there Hydrostatic and electrostatic intermolecular interactions
between insulin molecules which may keep these molecules
associated/aggregated enabling these to escape filteration/loss via
kidneys and stored or act for long time as per need?

Probably not under physiological conditions.

Whether diabetes or persisting hyperglycemia is a physiological
conditions?

Can't aggregation/assotiation or concentration of insulin molecules by
Hydrostatic and electrostatic intermolecular interactions AND by its
oligomerization be a natural body mechanism to control/balance/maintain
and store(either of these) insulin levels in blood--aggregation
somewhat medium acting and oligomerization somewhat long acting?

Quoted message said:

Again, insulin is
catabolized by the kidneys and not excreted.

Does it mean that it is filtered and lost its origional form as
degraded/denatured in kidneys(in loosing i am not counting reabsorption
of degraded/denatured form)? Or, it is degraded/denatured at other
parts(say liver) and filtered and lost in its degraded/denatured form?

Quoted message said:

Quoted message said:

Quoted message said:

The term polymerization, by definition, involves the formation of
covalent bonds.

Yes, thanks.

Again, you are welcome.

Quoted message said:

Quoted message said:

> > > In short does our body has any mechanism by
> > > which insulin can be stored and persit for longer time?
> >
> > No. If it did, insulin would lose its ability to signal.
> >
> Yes, but on getting diabeteswith IR, it looks alike as insulin is
> working lesser.

It still works as a signal even if less effectively.

Whether insulin loosing its ability to signal is due to aggregation of
its molecules?

Quoted message said:

Quoted message said:

It works less, whether due to receptor's regulations changes?

There is storage of insulin occurring in extracellular compartments.

How and in what form of insulin?

Quoted message said:

Quoted message said:

Quoted message said:

> > > > > What such more insulin can cause, how it will signal other actions?
> > > >
> > > > Through its receptors which when activated phosphorylates specific
> > > > intracellular proteins involved in increasing glucose uptake and
> > > > growth.
> > > It looks all actions of insulin is primarily glucose related. Ok?
> >
> > It also promotes growth.
> >
> How?

Through receptor-mediated post-translational modification (tyrosine
phosporylation) of intracellular proteins involved in cellular growth.

Thanks.

You are welcome :-)

You deserve. All people esp. those who accept sprituals+science belong
to LORD. We know we have spritual+scientific OR
sensations/psychlogical+ingestion/chemical/physiological effects OR
(cephalic+ingestion..pre-stomach+in stomach andpost-stomach) effects
but still we think less of sprituals.

Quoted message said:

All thanks and praises belong to the LORD, Whom I love with all my
heart, soul, mind, and strength :-))

Will be available to "glow" and chat about this and other things like
cardiology, diabetes, cooking and nutrition that interest those
following this thread here during the next on-line chat (02/02/06) from
6 to 7 pm EST:

http://tinyurl.com/cpayh

For those who are put off by the signature, my advance apologies for
how the LORD has reshaped me:

http://tinyurl.com/bgfqt

Prayerfully in Christ's love,

Andrew
http://tinyurl.com/8juld

Kumar said:

Andrew B. Chung said:

Kumar said:

Andrew B. Chung, MD/PhD wrote:
> Kumar wrote:
> > Is there any other resistance in transporting injected insulin to
> > vascular compartment?
>
> No.

Can insulin molecules in blood or at other compartment be aggregated or
associated by intermolecular forces without polymerization?

Yes.

Can you tell some more detail about it? What is medical condition named
for it?

Death (ie non-physiological)

Quoted message said:

Quoted message said:

Quoted message said:

If yes, can
this condition exist for long?

Perhaps if conditions are non-physiological.

Quoted message said:

> > What are these intermolecular interactions?
>
> Receptor binding.
>
Good thanks.

You are welcome :-)

Quoted message said:

> > > Actually, there is a genetic predisposition toward developing insulin
> > > resistance.
> > >
> > How then it is reversible by correcting obesity esp.in diabetics who
> > have not yet start taking insulin injections?
>
> By decreasing levels of inflammatory cytokines which are produced by
> visceral adipocytes.
>
How then there can be a genetic predisposition towards developing
insulin resistance?

There are a number of possibilities. One example is that it could
occur with the genetic predisposition to develop visceral adiposity.

To get fat depositions or visceral adiposity, whether digestive acidic
or alkaline secretions and balanced insulin secretions is needed to be
changed/imbalanced?

Overeating is necessary and sufficient for developing visceral
adiposity.

Quoted message said:

Can low gastric acid, excess bile and low bicarbonate cause excess
intestinal fats digestion and absorption?

Not when there has been no excess ingested.

Quoted message said:

Quoted message said:

Quoted message said:

Whether inflammatory cytokines which are produced by visceral
adipocytes is only reason to getting IR or all inflammatory responses
can cause insulin resistance and hyperglycemia(infections are already
indicated to increse blood glucose levels)?

Chronically elevated levels of inflammatory cytokines likely has the
potential for causing IR regardless of the primary cause.

Whether Chronically elevated levels of inflammatory cytokines can be
the only/main cause of getting IR?

It is the only cause we know of at the moment.

Quoted message said:

Quoted message said:

Quoted message said:

As such, can greater adiposity or obesity be treated as inflammatory
diseases?

Far wiser would be to address the primary reason for the
adiposity/obesity.

What is that? Is it taking excess glucose/fats?

Overeating.

Quoted message said:

Quoted message said:

Quoted message said:

> > > > Will then
> > > > insulin be normally effective to these new cells?
> > >
> > > Not in the setting of metabolic syndrome (MetS).

Does it indicate that it is due to genetic predisposition?

There is a genetic predisposition to develop MetS.

Can genetic predisostions in diabetes2 basically cause excess cravings
to foods resulting into more food intake>>more glucose>>more
insulin>>IR>>hyperglycemia....?

No. It lowers the threshold of amount of visceral adiposity before IR
occurs.

Quoted message said:

If yes, how this excess craving is oriented? Is it by genetic
predisposition to get excess gastric acid and insulin secretion?

No.

Quoted message said:

Quoted message said:

Quoted message said:

> > > > Can/does insulin polymerize at other comprtments than blood?
> > >
> > > Hydrostatic and electrostatic interactions do not involve the formation
> > > of covalent bonds necessary for polymerization.

Are there Hydrostatic and electrostatic intermolecular interactions
between insulin molecules which may keep these molecules
associated/aggregated enabling these to escape filteration/loss via
kidneys and stored or act for long time as per need?

Probably not under physiological conditions.

Whether diabetes or persisting hyperglycemia is a physiological
conditions?

In the absence of DKA, the conditions should remain physiological
through mechanisms that maintain homeostasis.

Quoted message said:

Can't aggregation/assotiation or concentration of insulin molecules by
Hydrostatic and electrostatic intermolecular interactions AND by its
oligomerization be a natural body mechanism to control/balance/maintain
and store(either of these) insulin levels in blood--aggregation
somewhat medium acting and oligomerization somewhat long acting?

No. Again, storage of insulin would disrupt its signalling function.

Quoted message said:

Quoted message said:

Again, insulin is
catabolized by the kidneys and not excreted.

Does it mean that it is filtered and lost its origional form as
degraded/denatured in kidneys(in loosing i am not counting reabsorption
of degraded/denatured form)? Or, it is degraded/denatured at other
parts(say liver) and filtered and lost in its degraded/denatured form?

It simply is not excreted but catabolized.

Quoted message said:

Quoted message said:

Quoted message said:

> The term polymerization, by definition, involves the formation of
> covalent bonds.

Yes, thanks.

Again, you are welcome.

Quoted message said:

> > > > In short does our body has any mechanism by
> > > > which insulin can be stored and persit for longer time?
> > >
> > > No. If it did, insulin would lose its ability to signal.
> > >
> > Yes, but on getting diabeteswith IR, it looks alike as insulin is
> > working lesser.
>
> It still works as a signal even if less effectively.

Whether insulin loosing its ability to signal is due to aggregation of
its molecules?

No. It occurs by a downregulation of its receptor number because of
the action of inflammatory cytokines.

Quoted message said:

Quoted message said:

Quoted message said:

It works less, whether due to receptor's regulations changes?

There is storage of insulin occurring in extracellular compartments.

How and in what form of insulin?

Sorry. That should have been that there is **no** storage of insulin
in extracellular compartments. There is storage of pro-insulin in
intracellular compartments.

Quoted message said:

Quoted message said:

Quoted message said:

> > > > > > What such more insulin can cause, how it will signal other actions?
> > > > >
> > > > > Through its receptors which when activated phosphorylates specific
> > > > > intracellular proteins involved in increasing glucose uptake and
> > > > > growth.
> > > > It looks all actions of insulin is primarily glucose related. Ok?
> > >
> > > It also promotes growth.
> > >
> > How?
>
> Through receptor-mediated post-translational modification (tyrosine
> phosporylation) of intracellular proteins involved in cellular growth.

Thanks.

You are welcome :-)

You deserve.

I deserve nothing but have been blessed with much through the LORD's
infinite mercy and grace.

However, thank you for the kind thoughts.

May the LORD bless you and yours today and everyday, in Jesus' most
precious and holy name :-)

Will be available to "glow" and chat about this and other things like
cardiology, diabetes, cooking and nutrition that interest those
following this thread here during the next on-line chat (02/02/06) from
6 to 7 pm EST:

http://tinyurl.com/cpayh

For those who are put off by the signature, my advance apologies for
how the LORD has reshaped me:

http://tinyurl.com/bgfqt

Prayerfully in Christ's love,

Andrew
http://tinyurl.com/8juld

Andrew B. Chung said:

Kumar said:

Andrew B. Chung said:

Kumar wrote:
> Andrew B. Chung, MD/PhD wrote:
> > Kumar wrote:
> > > Is there any other resistance in transporting injected insulin to
> > > vascular compartment?
> >
> > No.
>
> Can insulin molecules in blood or at other compartment be aggregated or
> associated by intermolecular forces without polymerization?

Yes.

Can you tell some more detail about it? What is medical condition named
for it?

Death (ie non-physiological)

What about in physiological imbalances? Can't something be other than
physiological and non-physiological? I consider it as physiological
imbalances as in diabetes, IR etc.

Quoted message said:

Quoted message said:

Quoted message said:

> If yes, can
> this condition exist for long?

Perhaps if conditions are non-physiological.

> > > What are these intermolecular interactions?
> >
> > Receptor binding.
> >
> Good thanks.

You are welcome :-)

> > > > Actually, there is a genetic predisposition toward developing insulin
> > > > resistance.
> > > >
> > > How then it is reversible by correcting obesity esp.in diabetics who
> > > have not yet start taking insulin injections?
> >
> > By decreasing levels of inflammatory cytokines which are produced by
> > visceral adipocytes.
> >
> How then there can be a genetic predisposition towards developing
> insulin resistance?

There are a number of possibilities. One example is that it could
occur with the genetic predisposition to develop visceral adiposity.

To get fat depositions or visceral adiposity, whether digestive acidic
or alkaline secretions and balanced insulin secretions is needed to be
changed/imbalanced?

Overeating is necessary and sufficient for developing visceral
adiposity.

Yes, but on overeating, can't imbalances in gastric acid, bile or
bicarbonate cause more or less digestions resulting into more or less
absoptions of fats?

Quoted message said:

Quoted message said:

Can low gastric acid, excess bile and low bicarbonate cause excess
intestinal fats digestion and absorption?

Not when there has been no excess ingested.

Oh you awnsered. It can be more or less due to digestive secretions?

Quoted message said:

Quoted message said:

Quoted message said:

> Whether inflammatory cytokines which are produced by visceral
> adipocytes is only reason to getting IR or all inflammatory responses
> can cause insulin resistance and hyperglycemia(infections are already
> indicated to increse blood glucose levels)?

Chronically elevated levels of inflammatory cytokines likely has the
potential for causing IR regardless of the primary cause.

Whether Chronically elevated levels of inflammatory cytokines can be
the only/main cause of getting IR?

It is the only cause we know of at the moment.

Thanks. Iron imbalances and relaxed conditions of blood
vessels(dilation) (may be swelling,acidosis,pain) look to be related to
inflammatory diseases. How these conditions can be related to adiposity
and getting inflammatory cytolines?

Quoted message said:

Quoted message said:

Quoted message said:

> As such, can greater adiposity or obesity be treated as inflammatory
> diseases?

Far wiser would be to address the primary reason for the
adiposity/obesity.

What is that? Is it taking excess glucose/fats?

Overeating.

Can exposure of various foods, easy cooking, easy availabilty of foods,
stress i.e. modern lifestyle in big cities and pollution can cause
excess cravings and overeating? If yes, will these cause excess gastric
acid and insulin secretions by somewhat "cephalic phase type effects?
Probably alike use of double bads may trigger readymade and excessive
urge to sit and sleep.

Accordingly are we either genetically predisposed to make such modern
lifestyle etc. imbalances or genetic predispositions in body's cells
towords getting the diseases? (just a thought).

Quoted message said:

Quoted message said:

Quoted message said:

> > > > > Will then
> > > > > insulin be normally effective to these new cells?
> > > >
> > > > Not in the setting of metabolic syndrome (MetS).
>
> Does it indicate that it is due to genetic predisposition?
>

There is a genetic predisposition to develop MetS.

Can genetic predisostions in diabetes2 basically cause excess cravings
to foods resulting into more food intake>>more glucose>>more
insulin>>IR>>hyperglycemia....?

No. It lowers the threshold of amount of visceral adiposity before IR
occurs.

Yes but how? Whether visceral adiposity is a natural body response to
protect organs in inflammatory conditions?

Quoted message said:

Quoted message said:

If yes, how this excess craving is oriented? Is it by genetic
predisposition to get excess gastric acid and insulin secretion?

No.

Or as above which I mentioned..modern lifestyle and atmosphere?

Btw, how getting diabetes2, IR and hypertentions are different in big
polluted and crowded cities and in clean environment remote and natural
areas of small villages or in jungles?

Quoted message said:

Quoted message said:

Quoted message said:

> > > > > Can/does insulin polymerize at other comprtments than blood?
> > > >
> > > > Hydrostatic and electrostatic interactions do not involve the formation
> > > > of covalent bonds necessary for polymerization.
>
> Are there Hydrostatic and electrostatic intermolecular interactions
> between insulin molecules which may keep these molecules
> associated/aggregated enabling these to escape filteration/loss via
> kidneys and stored or act for long time as per need?

Probably not under physiological conditions.

Whether diabetes or persisting hyperglycemia is a physiological
conditions?

In the absence of DKA, the conditions should remain physiological
through mechanisms that maintain homeostasis.

Yes but what about maintainable imbalances or in "not yet fatal"
conditions? We can have persistent hyperglycemia, fats depositions etc.
for many years still may not be "immediate fatal". I think these can be
catagerized as "physiological imbalances" instead of physiological or
non-physiological. ??

Quoted message said:

Quoted message said:

Can't aggregation/assotiation or concentration of insulin molecules by
Hydrostatic and electrostatic intermolecular interactions AND by its
oligomerization be a natural body mechanism to control/balance/maintain
and store(either of these) insulin levels in blood--aggregation
somewhat medium acting and oligomerization somewhat long acting?

No. Again, storage of insulin would disrupt its signalling function.

Yes, but some insulin can be stored for prolonged requirements due to
persitent hyperglycemia. This looks alike IR.

Btw, whether pacreas can continuously secrete insulin or need some time
to refill--in normal health and in diabetes2?

Quoted message said:

Quoted message said:

Quoted message said:

Again, insulin is
catabolized by the kidneys and not excreted.

Does it mean that it is filtered and lost its origional form as
degraded/denatured in kidneys(in loosing i am not counting reabsorption
of degraded/denatured form)? Or, it is degraded/denatured at other
parts(say liver) and filtered and lost in its degraded/denatured form?

It simply is not excreted but catabolized.

Ok, it looks like suspense. Cells uses insulin in kidney's area is a
different aspect but whether some insulin in reasonable quantity
effecting glucose levels in blood is lost via kidneys or not in normal
health or in some disease?

Quoted message said:

Quoted message said:

Quoted message said:

> > The term polymerization, by definition, involves the formation of
> > covalent bonds.
>
> Yes, thanks.

Again, you are welcome.

> > > > > In short does our body has any mechanism by
> > > > > which insulin can be stored and persit for longer time?
> > > >
> > > > No. If it did, insulin would lose its ability to signal.
> > > >
> > > Yes, but on getting diabeteswith IR, it looks alike as insulin is
> > > working lesser.
> >
> > It still works as a signal even if less effectively.
>

Whether insulin loosing its ability to signal is due to aggregation of
its molecules?

No. It occurs by a downregulation of its receptor number because of
the action of inflammatory cytokines.

Yes, thanks. Is there any medicine which can directly control these
inflammatory cytokines without controlling adiposity? NSAIDs??

Quoted message said:

Quoted message said:

Quoted message said:

> It works less, whether due to receptor's regulations changes?

There is storage of insulin occurring in extracellular compartments.

How and in what form of insulin?

Sorry. That should have been that there is **no** storage of insulin
in extracellular compartments. There is storage of pro-insulin in
intracellular compartments.

Ok, it shoked me at that time. Storage of pro-insulin in Intracellular
compartments--you mean only in pancreas?

Quoted message said:

Quoted message said:

Quoted message said:

> > > > > > What such more insulin can cause, how it will signal

other actions?

Quoted message said:

Quoted message said:

Quoted message said:

> > > > > >
> > > > > > Through its receptors which when activated phosphorylates specific
> > > > > > intracellular proteins involved in increasing glucose uptake and
> > > > > > growth.
> > > > > It looks all actions of insulin is primarily glucose related. Ok?
> > > >
> > > > It also promotes growth.
> > > >
> > > How?
> >
> > Through receptor-mediated post-translational modification (tyrosine
> > phosporylation) of intracellular proteins involved in cellular growth.
>
> Thanks.

You are welcome :-)

You deserve.

I deserve nothing but have been blessed with much through the LORD's
infinite mercy and grace.

However, thank you for the kind thoughts.

May the LORD bless you and yours today and everyday, in Jesus' most
precious and holy name :-)

Thanks for your kind blessings.

Quoted message said:

Will be available to "glow" and chat about this and other things like
cardiology, diabetes, cooking and nutrition that interest those
following this thread here during the next on-line chat (02/02/06) from
6 to 7 pm EST:

http://tinyurl.com/cpayh

For those who are put off by the signature, my advance apologies for
how the LORD has reshaped me:

http://tinyurl.com/bgfqt

Prayerfully in Christ's love,

Andrew
http://tinyurl.com/8juld

On Sat, 28 Jan 2006 08:29:33 -0600, "Ken Kubos" <[email hidden]>

Quoted message said:

Aaaaah the lord made an obsessive-compulsive (http://www.ocfoundation.org/)
little man!
Ken

"Buddhism elucidates why we are sentient."
"Karma means that you don't get away with anything."

Being made in God's image explains our sentience.

God's Grace means that we can "get away with" everything, provided
that we accept that Grace through Jesus Christ and are truly
repentant.

John

John said:

On Sat, 28 Jan 2006 08:29:33 -0600, "Ken Kubos" <[email hidden]>

Quoted message said:

Aaaaah the lord made an obsessive-compulsive (http://www.ocfoundation.org/)
little man!
Ken

"Buddhism elucidates why we are sentient."
"Karma means that you don't get away with anything."

Being made in God's image explains our sentience.

God's Grace means that we can "get away with" everything, provided
that we accept that Grace through Jesus Christ and are truly
repentant.

John

Amen and amen :-)

May the LORD continue to bless you and yours today and everyday, in
Jesus' most precious and holy name :-))

Will be available to "glow" and chat about this and other things like
cardiology, diabetes, cooking and nutrition that interest those
following this thread here during the next on-line chat (02/02/06) from
6 to 7 pm EST:

http://tinyurl.com/cpayh

For those who are put off by the signature, my advance apologies for
how the LORD has reshaped me:

http://tinyurl.com/bgfqt

Prayerfully in Christ's love,

Andrew
http://tinyurl.com/8juld

"Fat-Immune System-Inflammation Link
Your fat cells increase inflammation in another way, by attracting a
type of white blood cell known as a macrophage, which produces
inflammatory cytokines.(9) Macrophages are scavenger cells. Their job
is literally to gobble up foreign organisms and cellular debris.

Macrophages seem to be drawn to body fat because fat cells tend to leak
and break open, especially in people with abdominal obesity.
Macrophages move into the leaky fat tissue in order to clean up debris
and then they themselves begin to release inflammatory factors.
Macrophages appear to be a major contributor to inflammation.(
the relationship of diet, inflammation and weight is summarized here:

A diet high in refined carbohydrates and other "fabricated" foods leads
to both increased weight and increased inflammation.

Excess weight itself causes chronic inflammation.

Chronic inflammation contributes to more insulin resistance, leptin
resistance, and other metabolic disorders. It also decreases favorable
adiponectin and increases unfavorable resistin.

Insulin resistance and leptin resistance stimulate accumulation of more
weight, make weight loss more difficult, and induce hyperandrogenism
(excessive levels of male hormones) and other symptoms of PCOS.

The added weight induces more inflammation and thus more insulin and
leptin resistance, which in turn prevents you from burning off fat
stores, and causes you to store even more fat.
Here is the vicious cycle of obesity and leptin resistance: Extra fat
produces chronic, low-grade inflammation. The chronic inflammation
produces a chronic anti-inflammatory response, led by SOCS molecules.
The SOCS response stops leptin from reducing obesity. So weight goes
up, which causes more inflammation. And the cycle starts all over
again.
http://www.ovarian-cysts-pcos.com/inflammation.html#sec2 "

Whether IR happens in the way as mentioned on above link?

"In a normal person, a small amount of insulin is produced after eating
("postprandial"😉, and it signals the body to absorb the sugars from the
food at a steady rate. In an "insulin resistant" person the message
does not get to the cells so the sugar remains in the blood for long
periods of time while ever more insulin is released in an attempt to
trigger the sugar-uptake. The sugar circulates in the blood for several
hours and then is taken into the cells very rapidly, leading to a steep
drop in blood sugar and a hypoglycaemic reaction several hours after
the meal.

At a later stage, frank hyperglycemia develops as pancreatic ß-cells
are unable to produce adequate insulin to maintain normal blood sugar
levels ("euglycemia"😉.

Various disease states make the body tissues more resistant to the
actions of insulin. Example include infection (TNFa) and acidosis.
Recent research involves the relative roles of adipokines (the
cytokines produced by adipose tissue) in modifying insulin resistance
http://en.wikipedia.org/wiki/Insulin_resistance "

Glucose requirements may be more in case of getting infections and
inflammations. Infections and greater adiposity trigger inflammatory
responses so more need of energy/glucose. So these inflammatory
responses are meant to remove the cause of inflammations--adiposity anf
infections.

Can't such inflammatory responses treat greater adiposity, infections
etc. naturally? In view of this, How far it is correct to lower such
hyperglycemia by medications instead of correcting greater adiposity,
infections or inflammatory responses? Can't such interferances by
medications will not interfere in the natural treatment of these
inflammatory responses? What can be the results of such interferances
by medications?

Kumar said:

Andrew B. Chung said:

Kumar said:

Andrew B. Chung, MD/PhD wrote:
> Kumar wrote:
> > Andrew B. Chung, MD/PhD wrote:
> > > Kumar wrote:
> > > > Is there any other resistance in transporting injected insulin to
> > > > vascular compartment?
> > >
> > > No.
> >
> > Can insulin molecules in blood or at other compartment be aggregated or
> > associated by intermolecular forces without polymerization?
>
> Yes.

Can you tell some more detail about it? What is medical condition named
for it?

Death (ie non-physiological)

What about in physiological imbalances? Can't something be other than
physiological and non-physiological?

Yes... unstable.

Quoted message said:

I consider it as physiological
imbalances as in diabetes, IR etc.

Chronic conditions still result in a steady-state (homeostasis) which
will be physiological.

Quoted message said:

Quoted message said:

Quoted message said:

> > If yes, can
> > this condition exist for long?
>
> Perhaps if conditions are non-physiological.
>
> > > > What are these intermolecular interactions?
> > >
> > > Receptor binding.
> > >
> > Good thanks.
>
> You are welcome :-)
>
> > > > > Actually, there is a genetic predisposition toward developing insulin
> > > > > resistance.
> > > > >
> > > > How then it is reversible by correcting obesity esp.in diabetics who
> > > > have not yet start taking insulin injections?
> > >
> > > By decreasing levels of inflammatory cytokines which are produced by
> > > visceral adipocytes.
> > >
> > How then there can be a genetic predisposition towards developing
> > insulin resistance?
>
> There are a number of possibilities. One example is that it could
> occur with the genetic predisposition to develop visceral adiposity.

To get fat depositions or visceral adiposity, whether digestive acidic
or alkaline secretions and balanced insulin secretions is needed to be
changed/imbalanced?

Overeating is necessary and sufficient for developing visceral
adiposity.

Yes, but on overeating, can't imbalances in gastric acid, bile or
bicarbonate cause more or less digestions resulting into more or less
absoptions of fats?

In practice, no.

Quoted message said:

Quoted message said:

Quoted message said:

Can low gastric acid, excess bile and low bicarbonate cause excess
intestinal fats digestion and absorption?

Not when there has been no excess ingested.

Oh you awnsered. It can be more or less due to digestive secretions?

In practice, no.

Quoted message said:

Quoted message said:

Quoted message said:

> > Whether inflammatory cytokines which are produced by visceral
> > adipocytes is only reason to getting IR or all inflammatory responses
> > can cause insulin resistance and hyperglycemia(infections are already
> > indicated to increse blood glucose levels)?
>
> Chronically elevated levels of inflammatory cytokines likely has the
> potential for causing IR regardless of the primary cause.

Whether Chronically elevated levels of inflammatory cytokines can be
the only/main cause of getting IR?

It is the only cause we know of at the moment.

Thanks. Iron imbalances and relaxed conditions of blood
vessels(dilation) (may be swelling,acidosis,pain) look to be related to
inflammatory diseases. How these conditions can be related to adiposity
and getting inflammatory cytolines?

You are mixing up acute with chronic conditions.

Quoted message said:

Quoted message said:

Quoted message said:

> > As such, can greater adiposity or obesity be treated as inflammatory
> > diseases?
>
> Far wiser would be to address the primary reason for the
> adiposity/obesity.

What is that? Is it taking excess glucose/fats?

Overeating.

Can exposure of various foods, easy cooking, easy availabilty of foods,
stress i.e. modern lifestyle in big cities and pollution can cause
excess cravings and overeating?

Healthy people have healthy appetites (hunger and cravings).

Those who are afraid of hunger tend to overeat.

Those who are not afraid of hunger are able to avoid overeating.

The latter state of befriending hunger is an enlightened choice.

Quoted message said:

If yes, will these cause excess gastric
acid and insulin secretions by somewhat "cephalic phase type effects?
Probably alike use of double bads may trigger readymade and excessive
urge to sit and sleep.

Accordingly are we either genetically predisposed to make such modern
lifestyle etc. imbalances or genetic predispositions in body's cells
towords getting the diseases? (just a thought).

Overeating is a choice made out of fear of hunger.

Quoted message said:

Quoted message said:

Quoted message said:

> > > > > > Will then
> > > > > > insulin be normally effective to these new cells?
> > > > >
> > > > > Not in the setting of metabolic syndrome (MetS).
> >
> > Does it indicate that it is due to genetic predisposition?
> >
>
> There is a genetic predisposition to develop MetS.

Can genetic predisostions in diabetes2 basically cause excess cravings
to foods resulting into more food intake>>more glucose>>more
insulin>>IR>>hyperglycemia....?

No. It lowers the threshold of amount of visceral adiposity before IR
occurs.

Yes but how?

Through insulin receptor number, insulin binding affinity, baseline
levels of inflammatory cytokines, second messenger signalling pathways,
gene regulatory promoter elements, etc.

Quoted message said:

Whether visceral adiposity is a natural body response to
protect organs in inflammatory conditions?

No. Visceral adiposity is an unnatural condition arising from
overeating.

Quoted message said:

Quoted message said:

Quoted message said:

If yes, how this excess craving is oriented? Is it by genetic
predisposition to get excess gastric acid and insulin secretion?

No.

Or as above which I mentioned..modern lifestyle and atmosphere?

No. Hunger is a healthy state.

Quoted message said:

Btw, how getting diabetes2, IR and hypertentions are different in big
polluted and crowded cities and in clean environment remote and natural
areas of small villages or in jungles?

No difference.

Quoted message said:

Quoted message said:

Quoted message said:

> > > > > > Can/does insulin polymerize at other comprtments than blood?
> > > > >
> > > > > Hydrostatic and electrostatic interactions do not involve the formation
> > > > > of covalent bonds necessary for polymerization.
> >
> > Are there Hydrostatic and electrostatic intermolecular interactions
> > between insulin molecules which may keep these molecules
> > associated/aggregated enabling these to escape filteration/loss via
> > kidneys and stored or act for long time as per need?
>
> Probably not under physiological conditions.

Whether diabetes or persisting hyperglycemia is a physiological
conditions?

In the absence of DKA, the conditions should remain physiological
through mechanisms that maintain homeostasis.

Yes but what about maintainable imbalances or in "not yet fatal"
conditions?

Imbalances are not sustainable.

Quoted message said:

We can have persistent hyperglycemia, fats depositions etc.
for many years still may not be "immediate fatal". I think these can be
catagerized as "physiological imbalances" instead of physiological or
non-physiological. ??

No.

Quoted message said:

Quoted message said:

Quoted message said:

Can't aggregation/assotiation or concentration of insulin molecules by
Hydrostatic and electrostatic intermolecular interactions AND by its
oligomerization be a natural body mechanism to control/balance/maintain
and store(either of these) insulin levels in blood--aggregation
somewhat medium acting and oligomerization somewhat long acting?

No. Again, storage of insulin would disrupt its signalling function.

Yes, but some insulin can be stored for prolonged requirements due to
persitent hyperglycemia. This looks alike IR.

No.

Quoted message said:

Btw, whether pacreas can continuously secrete insulin or need some time
to refill--in normal health and in diabetes2?

The former.

Quoted message said:

Quoted message said:

Quoted message said:

>Again, insulin is
> catabolized by the kidneys and not excreted.

Does it mean that it is filtered and lost its origional form as
degraded/denatured in kidneys(in loosing i am not counting reabsorption
of degraded/denatured form)? Or, it is degraded/denatured at other
parts(say liver) and filtered and lost in its degraded/denatured form?

It simply is not excreted but catabolized.

Ok, it looks like suspense. Cells uses insulin in kidney's area is a
different aspect but whether some insulin in reasonable quantity
effecting glucose levels in blood is lost via kidneys or not in normal
health or in some disease?

There is no excretion of insulin by the kidneys. Intact insulin
polypeptide molecules are not present in the urine in significant
amounts in normal people.

Quoted message said:

Quoted message said:

Quoted message said:

> > > The term polymerization, by definition, involves the formation of
> > > covalent bonds.
> >
> > Yes, thanks.
>
> Again, you are welcome.
>
> > > > > > In short does our body has any mechanism by
> > > > > > which insulin can be stored and persit for longer time?
> > > > >
> > > > > No. If it did, insulin would lose its ability to signal.
> > > > >
> > > > Yes, but on getting diabeteswith IR, it looks alike as insulin is
> > > > working lesser.
> > >
> > > It still works as a signal even if less effectively.
> >

Whether insulin loosing its ability to signal is due to aggregation of
its molecules?

No. It occurs by a downregulation of its receptor number because of
the action of inflammatory cytokines.

Yes, thanks. Is there any medicine which can directly control these
inflammatory cytokines without controlling adiposity?

No.

Quoted message said:

NSAIDs??

No.

Why look for medicine when permanent weight loss cures this?

http://www.HeartMDPhD.com/wtloss.asp

Quoted message said:

Quoted message said:

Quoted message said:

> > It works less, whether due to receptor's regulations changes?
>
> There is storage of insulin occurring in extracellular compartments.

How and in what form of insulin?

Sorry. That should have been that there is **no** storage of insulin
in extracellular compartments. There is storage of pro-insulin in
intracellular compartments.

Ok, it shoked me at that time. Storage of pro-insulin in Intracellular
compartments--you mean only in pancreas?

Specifically, only in the beta islet cells of the pancreas.

Quoted message said:

Quoted message said:

Quoted message said:

> > > > > > > What such more insulin can cause, how it will signal

other actions?

Quoted message said:

Quoted message said:

> > > > > > >
> > > > > > > Through its receptors which when activated phosphorylates specific
> > > > > > > intracellular proteins involved in increasing glucose uptake and
> > > > > > > growth.
> > > > > > It looks all actions of insulin is primarily glucose related. Ok?
> > > > >
> > > > > It also promotes growth.
> > > > >
> > > > How?
> > >
> > > Through receptor-mediated post-translational modification (tyrosine
> > > phosporylation) of intracellular proteins involved in cellular growth.
> >
> > Thanks.
>
> You are welcome :-)
>
You deserve.

I deserve nothing but have been blessed with much through the LORD's
infinite mercy and grace.

However, thank you for the kind thoughts.

May the LORD bless you and yours today and everyday, in Jesus' most
precious and holy name :-)

Thanks for your kind blessings.

The blessings are HIS.

All thanks and praises belong to the LORD, Whom I love with all my
heart, soul, mind, and strength :-))

Will be available to "glow" and chat about this and other things like
cardiology, diabetes, cooking and nutrition that interest those
following this thread here during the next on-line chat (02/02/06) from
6 to 7 pm EST:

http://tinyurl.com/cpayh

For those who are put off by the signature, my advance apologies for
how the LORD has reshaped me:

http://tinyurl.com/bgfqt

Prayerfully in Christ's love,

Andrew
http://tinyurl.com/8juld

Andrew B. Chung said:

Kumar said:

Quoted message said:

> > > Whether inflammatory cytokines which are produced by visceral
> > > adipocytes is only reason to getting IR or all inflammatory responses
> > > can cause insulin resistance and hyperglycemia(infections are already
> > > indicated to increse blood glucose levels)?
> >
> > Chronically elevated levels of inflammatory cytokines likely has the
> > potential for causing IR regardless of the primary cause.
>
> Whether Chronically elevated levels of inflammatory cytokines can be
> the only/main cause of getting IR?

It is the only cause we know of at the moment.

Thanks. Iron imbalances and relaxed conditions of blood
vessels(dilation) (may be swelling,acidosis,pain) look to be related to
inflammatory diseases. How these conditions can be related to adiposity
and getting inflammatory cytolines?

You are mixing up acute with chronic conditions.

Is there any relation between iron imbalance and IR/hyperglycemia?

Quoted message said:

Quoted message said:

Quoted message said:

> > > As such, can greater adiposity or obesity be treated as inflammatory
> > > diseases?
> >
> > Far wiser would be to address the primary reason for the
> > adiposity/obesity.
>
> What is that? Is it taking excess glucose/fats?

Overeating.

Can exposure of various foods, easy cooking, easy availabilty of foods,
stress i.e. modern lifestyle in big cities and pollution can cause
excess cravings and overeating?

Healthy people have healthy appetites (hunger and cravings).

Those who are afraid of hunger tend to overeat.

Those who are not afraid of hunger are able to avoid overeating.

The latter state of befriending hunger is an enlightened choice.

Who are afraid of hunger?

..

Quoted message said:

Quoted message said:

Quoted message said:

> > > > > > > Will then
> > > > > > > insulin be normally effective to these new cells?
> > > > > >
> > > > > > Not in the setting of metabolic syndrome (MetS).
> > >
> > > Does it indicate that it is due to genetic predisposition?
> > >
> >
> > There is a genetic predisposition to develop MetS.
>
> Can genetic predisostions in diabetes2 basically cause excess cravings
> to foods resulting into more food intake>>more glucose>>more
> insulin>>IR>>hyperglycemia....?

No. It lowers the threshold of amount of visceral adiposity before IR
occurs.

Yes but how?

Through insulin receptor number, insulin binding affinity, baseline
levels of inflammatory cytokines, second messenger signalling pathways,
gene regulatory promoter elements, etc.

Quoted message said:

Whether visceral adiposity is a natural body response to
protect organs in inflammatory conditions?

No. Visceral adiposity is an unnatural condition arising from
overeating.

If insulin resistant patient left untreated for diabetic medications,
can inflammatory cytokines/responses treat visceral adiposity?

Quoted message said:

Quoted message said:

Quoted message said:

> If yes, how this excess craving is oriented? Is it by genetic
> predisposition to get excess gastric acid and insulin secretion?

No.

Or as above which I mentioned..modern lifestyle and atmosphere?

No. Hunger is a healthy state.

What about craving in diabetic patients, eg; alcoholic patient's
craving for alcohol?

Quoted message said:

Quoted message said:

Btw, how getting diabetes2, IR and hypertentions are different in big
polluted and crowded cities and in clean environment remote and natural
areas of small villages or in jungles?

No difference.

Many time diabetic patient(myself also) find that his persistent higher
glucose in blood is well controlled inspite of taking excess food and
similar activities on visiting some remote/green area. ??

Quoted message said:

Quoted message said:

Quoted message said:

> Can't aggregation/assotiation or concentration of insulin molecules by
> Hydrostatic and electrostatic intermolecular interactions AND by its
> oligomerization be a natural body mechanism to control/balance/maintain
> and store(either of these) insulin levels in blood--aggregation
> somewhat medium acting and oligomerization somewhat long acting?

No. Again, storage of insulin would disrupt its signalling function.

Yes, but some insulin can be stored for prolonged requirements due to
persitent hyperglycemia. This looks alike IR.

No.

Quoted message said:

Btw, whether pacreas can continuously secrete insulin or need some time
to refill--in normal health and in diabetes2?

The former.

Thanks.

Quoted message said:

Quoted message said:

Quoted message said:

> >Again, insulin is
> > catabolized by the kidneys and not excreted.
>
> Does it mean that it is filtered and lost its origional form as
> degraded/denatured in kidneys(in loosing i am not counting reabsorption
> of degraded/denatured form)? Or, it is degraded/denatured at other
> parts(say liver) and filtered and lost in its degraded/denatured form?

It simply is not excreted but catabolized.

Ok, it looks like suspense. Cells uses insulin in kidney's area is a
different aspect but whether some insulin in reasonable quantity
effecting glucose levels in blood is lost via kidneys or not in normal
health or in some disease?

There is no excretion of insulin by the kidneys. Intact insulin
polypeptide molecules are not present in the urine in significant
amounts in normal people.

What about insulin is lost in urine in degraded or deformed form(not
intact) effected by more acidic/alkaline environment as present in
kidneys/bladder? I mean insulin is filtered intact but lost its intact
form in urine so not traced in urine?

Quoted message said:

Quoted message said:

Yes, thanks. Is there any medicine which can directly control these
inflammatory cytokines without controlling adiposity?

No.

Quoted message said:

NSAIDs??

No.

Why look for medicine when permanent weight loss cures this?

http://www.HeartMDPhD.com/wtloss.asp

Thanks.

Btw, can insulin cause hypertention, low HDL, high trigycerides in
blood--- due to its effect on fats depositions?

Kumar said:

Andrew B. Chung said:

Kumar said:

> > > > Whether inflammatory cytokines which are produced by visceral
> > > > adipocytes is only reason to getting IR or all inflammatory responses
> > > > can cause insulin resistance and hyperglycemia(infections are already
> > > > indicated to increse blood glucose levels)?
> > >
> > > Chronically elevated levels of inflammatory cytokines likely has the
> > > potential for causing IR regardless of the primary cause.
> >
> > Whether Chronically elevated levels of inflammatory cytokines can be
> > the only/main cause of getting IR?
>
> It is the only cause we know of at the moment.

Thanks. Iron imbalances and relaxed conditions of blood
vessels(dilation) (may be swelling,acidosis,pain) look to be related to
inflammatory diseases. How these conditions can be related to adiposity
and getting inflammatory cytolines?

You are mixing up acute with chronic conditions.

Is there any relation between iron imbalance and IR/hyperglycemia?

Iron overload can cause beta islet cell loss.

Quoted message said:

Quoted message said:

Quoted message said:

> > > > As such, can greater adiposity or obesity be treated as inflammatory
> > > > diseases?
> > >
> > > Far wiser would be to address the primary reason for the
> > > adiposity/obesity.
> >
> > What is that? Is it taking excess glucose/fats?
>
> Overeating.
>
Can exposure of various foods, easy cooking, easy availabilty of foods,
stress i.e. modern lifestyle in big cities and pollution can cause
excess cravings and overeating?

Healthy people have healthy appetites (hunger and cravings).

Those who are afraid of hunger tend to overeat.

Those who are not afraid of hunger are able to avoid overeating.

The latter state of befriending hunger is an enlightened choice.

Who are afraid of hunger?

Many are without being aware of it.

Quoted message said:

Quoted message said:

Quoted message said:

> > > > > > > > Will then
> > > > > > > > insulin be normally effective to these new cells?
> > > > > > >
> > > > > > > Not in the setting of metabolic syndrome (MetS).
> > > >
> > > > Does it indicate that it is due to genetic predisposition?
> > > >
> > >
> > > There is a genetic predisposition to develop MetS.
> >
> > Can genetic predisostions in diabetes2 basically cause excess cravings
> > to foods resulting into more food intake>>more glucose>>more
> > insulin>>IR>>hyperglycemia....?
>
> No. It lowers the threshold of amount of visceral adiposity before IR
> occurs.
>
Yes but how?

Through insulin receptor number, insulin binding affinity, baseline
levels of inflammatory cytokines, second messenger signalling pathways,
gene regulatory promoter elements, etc.

Quoted message said:

Whether visceral adiposity is a natural body response to
protect organs in inflammatory conditions?

No. Visceral adiposity is an unnatural condition arising from
overeating.

If insulin resistant patient left untreated for diabetic medications,
can inflammatory cytokines/responses treat visceral adiposity?

No. Only eating less reduces visceral adiposity.

Quoted message said:

Quoted message said:

Quoted message said:

> > If yes, how this excess craving is oriented? Is it by genetic
> > predisposition to get excess gastric acid and insulin secretion?
>
> No.
>

Or as above which I mentioned..modern lifestyle and atmosphere?

No. Hunger is a healthy state.

What about craving in diabetic patients, eg; alcoholic patient's
craving for alcohol?

Craving is a healthy state. Fear of the craving is what leads to
worsening diabetes and worsening alcoholism.

Quoted message said:

Quoted message said:

Quoted message said:

Btw, how getting diabetes2, IR and hypertentions are different in big
polluted and crowded cities and in clean environment remote and natural
areas of small villages or in jungles?

No difference.

Many time diabetic patient(myself also) find that his persistent higher
glucose in blood is well controlled inspite of taking excess food and
similar activities on visiting some remote/green area. ??

Estimates of amount of food ingested are not reliable especially for
folks who are in stressful environments (crowds, hustle and bustle)
which tend to increase hunger.

Quoted message said:

Quoted message said:

Quoted message said:

> > Can't aggregation/assotiation or concentration of insulin molecules by
> > Hydrostatic and electrostatic intermolecular interactions AND by its
> > oligomerization be a natural body mechanism to control/balance/maintain
> > and store(either of these) insulin levels in blood--aggregation
> > somewhat medium acting and oligomerization somewhat long acting?
>
> No. Again, storage of insulin would disrupt its signalling function.
>

Yes, but some insulin can be stored for prolonged requirements due to
persitent hyperglycemia. This looks alike IR.

No.

Quoted message said:

Btw, whether pacreas can continuously secrete insulin or need some time
to refill--in normal health and in diabetes2?

The former.

Thanks.

Quoted message said:

Quoted message said:

> > >Again, insulin is
> > > catabolized by the kidneys and not excreted.
> >
> > Does it mean that it is filtered and lost its origional form as
> > degraded/denatured in kidneys(in loosing i am not counting reabsorption
> > of degraded/denatured form)? Or, it is degraded/denatured at other
> > parts(say liver) and filtered and lost in its degraded/denatured form?
>
> It simply is not excreted but catabolized.
>
Ok, it looks like suspense. Cells uses insulin in kidney's area is a
different aspect but whether some insulin in reasonable quantity
effecting glucose levels in blood is lost via kidneys or not in normal
health or in some disease?

There is no excretion of insulin by the kidneys. Intact insulin
polypeptide molecules are not present in the urine in significant
amounts in normal people.

What about insulin is lost in urine in degraded or deformed form(not
intact) effected by more acidic/alkaline environment as present in
kidneys/bladder? I mean insulin is filtered intact but lost its intact
form in urine so not traced in urine?

There are no proteases in urine that would degrade insulin.

Quoted message said:

Quoted message said:

Quoted message said:

Yes, thanks. Is there any medicine which can directly control these
inflammatory cytokines without controlling adiposity?

No.

Quoted message said:

NSAIDs??

No.

Why look for medicine when permanent weight loss cures this?

http://www.HeartMDPhD.com/wtloss.asp

Thanks.

You are welcome :-)

Quoted message said:

Btw, can insulin cause hypertention, low HDL, high trigycerides in
blood--- due to its effect on fats depositions?

If it could, everyone would have hypertension, low HDL, and high
triglycerides except type I diabetics **before** insulin therapy.

Will be available to "glow" and chat about this and other things like
cardiology, diabetes, cooking and nutrition that interest those
following this thread here during the next on-line chat (02/02/06) from
6 to 7 pm EST:

http://tinyurl.com/cpayh

For those who are put off by the signature, my advance apologies for
how the LORD has reshaped me:

http://tinyurl.com/bgfqt

Prayerfully in Christ's love,

Andrew
http://tinyurl.com/8juld

Andrew B. Chung said:

Kumar said:

Andrew B. Chung said:

Kumar wrote:

> > > > > Whether inflammatory cytokines which are produced by visceral
> > > > > adipocytes is only reason to getting IR or all inflammatory responses
> > > > > can cause insulin resistance and hyperglycemia(infections are already
> > > > > indicated to increse blood glucose levels)?
> > > >
> > > > Chronically elevated levels of inflammatory cytokines likely has the
> > > > potential for causing IR regardless of the primary cause.
> > >
> > > Whether Chronically elevated levels of inflammatory cytokines can be
> > > the only/main cause of getting IR?
> >
> > It is the only cause we know of at the moment.
>
> Thanks. Iron imbalances and relaxed conditions of blood
> vessels(dilation) (may be swelling,acidosis,pain) look to be related to
> inflammatory diseases. How these conditions can be related to adiposity
> and getting inflammatory cytolines?

You are mixing up acute with chronic conditions.

Is there any relation between iron imbalance and IR/hyperglycemia?

Iron overload can cause beta islet cell loss.

Whether excess gastric acid secretion is related to iron overload due
to better digestion of iron containing foods(other than non-veg/iron
supplements) so better absorption? Can excess acid cause overriding of
intestinal mucus lining resulting into more iron absorption??

Quoted message said:

Quoted message said:

Quoted message said:

> > > > > As such, can greater adiposity or obesity be treated as inflammatory
> > > > > diseases?
> > > >
> > > > Far wiser would be to address the primary reason for the
> > > > adiposity/obesity.
> > >
> > > What is that? Is it taking excess glucose/fats?
> >
> > Overeating.
> >
> Can exposure of various foods, easy cooking, easy availabilty of foods,
> stress i.e. modern lifestyle in big cities and pollution can cause
> excess cravings and overeating?

Healthy people have healthy appetites (hunger and cravings).

Those who are afraid of hunger tend to overeat.

Those who are not afraid of hunger are able to avoid overeating.

The latter state of befriending hunger is an enlightened choice.

Who are afraid of hunger?

Many are without being aware of it.

It is due to more insulin secretion(probably more gastric acid
secretion also) in diabetic2 patients?

Quoted message said:

Quoted message said:

Quoted message said:

> > > > > > > > > Will then
> > > > > > > > > insulin be normally effective to these new cells?
> > > > > > > >
> > > > > > > > Not in the setting of metabolic syndrome (MetS).
> > > > >
> > > > > Does it indicate that it is due to genetic predisposition?
> > > > >
> > > >
> > > > There is a genetic predisposition to develop MetS.
> > >
> > > Can genetic predisostions in diabetes2 basically cause excess cravings
> > > to foods resulting into more food intake>>more glucose>>more
> > > insulin>>IR>>hyperglycemia....?
> >
> > No. It lowers the threshold of amount of visceral adiposity before IR
> > occurs.
> >
> Yes but how?

Through insulin receptor number, insulin binding affinity, baseline
levels of inflammatory cytokines, second messenger signalling pathways,
gene regulatory promoter elements, etc.

> Whether visceral adiposity is a natural body response to
> protect organs in inflammatory conditions?

No. Visceral adiposity is an unnatural condition arising from
overeating.

If insulin resistant patient left untreated for diabetic medications,
can inflammatory cytokines/responses treat visceral adiposity?

No. Only eating less reduces visceral adiposity.

Can eating more carbs(not fats) be only relared to getting greater
visceral adiposity?
Do we have insulin resistance to fat stores--may be by producing more
adipokines (the cytokines produced by adipose tissue)? Why body opt to
getting visceral adiposity instead of subcutnous?

Quoted message said:

Quoted message said:

Quoted message said:

> > > If yes, how this excess craving is oriented? Is it by genetic
> > > predisposition to get excess gastric acid and insulin secretion?
> >
> > No.
> >
>
> Or as above which I mentioned..modern lifestyle and atmosphere?

No. Hunger is a healthy state.

What about craving in diabetic patients, eg; alcoholic patient's
craving for alcohol?

Craving is a healthy state. Fear of the craving is what leads to
worsening diabetes and worsening alcoholism.

I really don't follow "fear of craving or fear of hunger". Is it due to
cells not getting enough glucose?

Quoted message said:

Quoted message said:

Quoted message said:

> Btw, how getting diabetes2, IR and hypertentions are different in big
> polluted and crowded cities and in clean environment remote and natural
> areas of small villages or in jungles?

No difference.

Many time diabetic patient(myself also) find that his persistent higher
glucose in blood is well controlled inspite of taking excess food and
similar activities on visiting some remote/green area. ??

Estimates of amount of food ingested are not reliable especially for
folks who are in stressful environments (crowds, hustle and bustle)
which tend to increase hunger.

How it tends to increase hunger?

Quoted message said:

Quoted message said:

Quoted message said:

> > > Can't aggregation/assotiation or concentration of insulin molecules by
> > > Hydrostatic and electrostatic intermolecular interactions AND by its
> > > oligomerization be a natural body mechanism to control/balance/maintain
> > > and store(either of these) insulin levels in blood--aggregation
> > > somewhat medium acting and oligomerization somewhat long acting?
> >
> > No. Again, storage of insulin would disrupt its signalling function.
> >
>
> Yes, but some insulin can be stored for prolonged requirements due to
> persitent hyperglycemia. This looks alike IR.

No.

> Btw, whether pacreas can continuously secrete insulin or need some time
> to refill--in normal health and in diabetes2?

The former.

Thanks.

Quoted message said:

>
> > > >Again, insulin is
> > > > catabolized by the kidneys and not excreted.
> > >
> > > Does it mean that it is filtered and lost its origional form as
> > > degraded/denatured in kidneys(in loosing i am not counting reabsorption
> > > of degraded/denatured form)? Or, it is degraded/denatured at other
> > > parts(say liver) and filtered and lost in its degraded/denatured form?
> >
> > It simply is not excreted but catabolized.
> >
> Ok, it looks like suspense. Cells uses insulin in kidney's area is a
> different aspect but whether some insulin in reasonable quantity
> effecting glucose levels in blood is lost via kidneys or not in normal
> health or in some disease?

There is no excretion of insulin by the kidneys. Intact insulin
polypeptide molecules are not present in the urine in significant
amounts in normal people.

What about insulin is lost in urine in degraded or deformed form(not
intact) effected by more acidic/alkaline environment as present in
kidneys/bladder? I mean insulin is filtered intact but lost its intact
form in urine so not traced in urine?

There are no proteases in urine that would degrade insulin.

Thanks.

Quoted message said:

Quoted message said:

Btw, can insulin cause hypertention, low HDL, high trigycerides in
blood--- due to its effect on fats depositions?

If it could, everyone would have hypertension, low HDL, and high
triglycerides except type I diabetics **before** insulin therapy.

Yes but can't more insulin--medicated or natural which is not used in
IR cases, cause it?

"Various disease states make the body tissues more resistant to the
actions of insulin. Example include infection (TNFa) and **acidosis**.
Recent research involves the relative roles of adipokines (the
cytokines produced by adipose tissue) in modifying insulin resistance.
http://en.wikipedia.org/wiki/Insulin_resistance "

This link suggest acidosis as one cause for insulin resistance. Is it
right? If yes, how it happens?

Andrew B. Chung said:

Quoted message said:

What about insulin is lost in urine in degraded or deformed form(not
intact) effected by more acidic/alkaline environment as present in
kidneys/bladder? I mean insulin is filtered intact but lost its intact
form in urine so not traced in urine?

There are no proteases in urine that would degrade insulin.

Continuance to last post....

Can it happen in following indicated manner:-

"The resulting highly acidic environment in the stomach lumen causes
proteins from food to lose their characteristic folded structure (or
denature). This exposes the protein's peptide bonds.
http://en.wikipedia.org/wiki/Gastric_acid "

Moreover can't fate of proteases in urine be alike of insulin or these
are reabsorbed so not traced in intact form?