"Diarmid Logan" <[email hidden]> wrote in message
"]news:[email hidden]...
Quoted message said:nature.com040510 5.htmlOpen ↗
Corn syrup linked to diabetes
HuaKul posted some very provocative information re type II
diabetes and fructose back in 2002. I saved the post, and
have reproduced it below. Quite interesting, and suggests
possible mechanisms for the role too much fructose may play
in fattening us up, as well as promoting diabetes. The below
is his post in full, including abstracts:
==================================================================
Fructose is worse than just an added sugar. The following
article shows that rats deficient in a protein called
insulin receptor substrate-2 become obese and diabetic. The
abstract summary that follows shows that IRS-2 is
significantly reduced by fructose, more than sucrose. In
1976 the US soft drink companies started using high fructose
corn sweetener because it was cheaper than using sucrose,
and by 1980 the switch was complete. Other processed food
manufacturers followed suit, and now fructose is ubiquitous.
One almost can't find a processed food without fructose;
soda pop, salad dressings, baked goods, even some fruit
juices are sweetened with fructose. At the same time the US
media and medical spokesmen lament the T2 diabetes and
obesity "epidemic," especially among juveniles, that they
claim started in 1980. No one is making the connection, but
it seems obvious to me that fructose as a sweetener is the
culprit. It's very normal for US teens to drink 2 liters or
more of soda pop each day. That's over 200g of pure
fructose. This is on top of all the junk food and bakery
they also eat, sweetened with fructose.
========================================================
"Researchers Find Common Link Between Diabetes, Obesity and
Infertility Joslin Diabetes Center AScribe Newswire -
September 20, 2000
BOSTON, Sept. 20 (AScribe News) -- Research published in
this week's issue of the journal Nature shows that insulin
receptor substrate-2 (IRS-2), a protein inside of cells that
is essential for normal response to insulin, might also
promote fertility and fight against obesity.
The study shows that female mice lacking the IRS-2 gene
rarely become pregnant, consume more food, and become fat.
"IRS-2 is like a switchboard that coordinates appetite, fat
storage, and blood glucose together with energy demanding
processes like reproduction, development, and tissue
repair," says Morris F. White, Ph.D., of the Joslin Diabetes
Center and the Howard Hughes Medical Institute.
Two years ago, a group of scientists led by Dr. White
discovered that IRS-2 is required not only for normal
insulin action, but also promotes the survival of pancreatic
beta cells that secrete insulin into the blood. Insulin
action and secretion are two of the important processes that
fail in people with type 2 diabetes, and never before was
the link between insulin use and production so closely
established. Now, the addition of obesity and reproduction
to the list of processes regulated by IRS-2 suggests that
type 2 diabetes and its association with obesity, reduced
fertility, and other complications might share a common
molecular defect.
Dr. White's group began to study IRS-2 in mice because it
helps them understand the problems that occur during
type 2 diabetes. Type 2 diabetes is an increasingly
common disease that occurs in people when the cells in
the liver, muscle and fat require more insulin to
control blood glucose than the pancreatic beta cells can
make. When IRS-2 is present and working, surprisingly
low levels of insulin can keep blood glucose under
control. But like people with type 2 diabetes,
genetically altered mice lacking IRS-2 need more insulin
and eventually develop diabetes, not because the insulin
resistance is so severe, but because their pancreatic
islets fail to make enough insulin to keep up with the
greater demand.
"IRS-2 failure is a double-edged sword," says Dr. White,
"because IRS-2 is needed so peripheral tissues can use
insulin, and needed to help keep pancreatic beta cells
alive longer so they can secrete more insulin to the
resistant tissues."
Female mice lacking IRS-2 develop diabetes between 18-20
weeks of age, much later in life than their male
counterparts who die of diabetic complications around 10
weeks of age. But long before the female mice develop
diabetes, they over-eat and become obese, and have reduced
fertility.
"In the beginning, these findings surprised us," says
Deborah J. Burks, Ph.D., of Joslin and the lead author of
the study, "but now we're beginning to appreciate that the
IRS-2 branch of the insulin signaling pathway might have an
important job in the brain to help coordinate food intake
and promote reproduction."
The IRS-2-deficient mice over-eat despite the presence of
excess amounts of leptin in their blood. Leptin is a protein
produced in fat cells that circulates to the hypothalamus, a
special region of the brain, to suppress appetite. However,
without IRS-2, female mice respond weakly to the appetite-
suppressing effects of leptin, and thus over-eat and gain
weight until enough leptin is finally produced to suppress
their appetite. Since IRS-2 molecules transmit insulin
signals within cells, these studies suggest that insulin
itself might participate in the regulation of food intake.
The ability of the brain to detect and respond to blood
insulin levels has been controversial for decades, but these
results and other recent evidence suggest that to regulate
appetite the brain must detect circulating insulin.
Scientists and clinicians have known for a long time that
obesity and chronic insulin resistance go hand-in-hand, but
they usually say that obesity causes insulin resistance.
That's one of the reasons why obesity is said to be a risk
factor for type 2 diabetes. But evidence in this study
suggests that it could be the other way around, with insulin
resistance initially dysregulating appetite that contributes
to obesity. The developing obesity exacerbates the insulin
resistance, which further burdens the pancreatic beta cells.
"It appears that IRS-2 helps coordinates insulin production
and nutrient metabolism to promote important biological
processes that reflect our health and fitness such as
appetite and fertility," Dr. Burks says. Female mice without
IRS-2 have a difficult time getting pregnant weeks before
they develop diabetes. The root of this deficiency begins
before birth, as ovaries in IRS-2 deficient mice develop
fewer primary oocytes. But in adults, the reproductive cycle
fails, not only because the ovaries are small and
unresponsive to gonadotropins, but also because cells in the
pituitary secrete less of these hormones. Clinicians have
known for years that women with polycystic ovarian syndrome
(PCOS) are frequently obese, but they are starting to
realize that these infertile women are usually insulin
resistant. This combination of endocrine disorders might be
related through the action of IRS-2.
"Type 2 diabetes is more than a problem with blood glucose,"
Dr. White says. "High blood glucose is the easiest thing to
measure, but the underlying cause might reside in the IRS-2
branch of the insulin-signaling pathway. You can live with
reduced IRS-2 function, but you might be glucose intolerant,
over-eat and gain weight; have a difficult time becoming
pregnant and when you do, develop gestational diabetes; and
worst of all, face life with pancreatic beta cells that
eventually fail to make enough insulin to avoid the life-
threatening consequences of type 2 diabetes."
Standard treatments for diabetes don't target IRS-2
signaling. "Given the critical role of this molecule in the
maintenance of glucose homeostasis and reproduction, it
might be ideal to develop new drugs to repair IRS-2
function," say the researchers, "because these therapies
might reduce weight gain and the amount of insulin needed in
the body while ensuring adequate insulin production
throughout life." AScribe - The Public Interest Newswire /
510-645-4600"
================================================
Braz J Med Biol Res 2000 Dec;33(12):1421-7 A high-fructose
diet induces changes in pp185 phosphorylation in muscle and
liver of rats. Ueno M, Bezerra RM, Silva MS, Tavares DQ,
Carvalho CR, Saad MJ Departamento de Planejamento Alimentar
e Nutricao, Faculdade de Engenharia de Alimentos,
Universidade Estadual de Campinas, Campinas, SP, Brasil.
Insulin stimulates the tyrosine kinase activity of its
receptor resulting in the tyrosine phosphorylation of pp185,
which contains insulin receptor substrates IRS-1 and IRS-2.
These early steps in insulin action are essential for the
metabolic effects of insulin. Feeding animals a high-
fructose diet results in insulin resistance. However, the
exact molecular mechanism underlying this effect is unknown.
In the present study, we determined the levels and
phosphorylation status of the insulin receptor and pp185 (IRS-
(1/2)) in liver and muscle of rats submitted to a high-
fructose diet evaluated by immunoblotting with specific
antibodies. Feeding fructose (28 days) induced a discrete
insulin resistance, as demonstrated by the insulin tolerance
test. Plasma glucose and serum insulin and cholesterol
levels of the two groups of rats, fructose-fed and control,
were similar, whereas plasma triacylglycerol concentration
was significantly increased in the rats submitted to the
fructose diet (P<0.05). There were no changes in insulin
receptor concentration in the liver or muscle of either
group. However, insulin-stimulated receptor
autophosphorylation was reduced to 72 /- 4% (P<0.05) in the
liver of high-fructose rats. The IRS-1 protein levels were
similar in both liver and muscle of the two groups of rats.
In contrast, there was a significant decrease in insulin-
induced pp185 (IRS-(1/2)) phosphorylation, to 83 /- 5%
(P<0.05) in liver and to 77 /- 4% (P<0.05) in muscle of the
high-fructose rats. These data suggest that changes in the
early steps of insulin signal transduction may have an
important role in the insulin resistance induced by high-
fructose feeding. PMID: 11105093
=========================================================
--Hua Kul
