"minerva nine" <
[email protected]> wrote in message
news:[email protected]...
> > M9:Fructose is tricky in that although it is a refined
> > sugar, it does not invoke much insulin response,
> > satiety etc. It is said to bypass normal glucose
> > regulatory response and to be processed mainly by the
> > liver
> directly
> > into fats.
>
> OK, if it doesn't invoke much insulin response, how does
> it contribute to insulin resistance? I've read the
> articles, but they're pretty technical, so a "for dummies"
> explanation would be appreciated. Thanks -- M9
>
>
As a recognized non-expert, my opinion is worth what you pay
for it. It is constantly in a state of revision. With Hua
Kul's posts some of this is redundant. Maybe it will serve
as a sort of summary.
Insulin resistance is known to be complex and
multifactorial; research has been very animal dependent, and
much more remains to be done. Persistent insulin resistance
does not necessarily imply that you will eventually become
diabetic. It probably does imply that you will become
overweight or obese. (some still suggest that gluttony and
obesity come before IR) After genetics, current evidence
tends to point to influences which affect or bypass appetite
regulation. As an example, triaglycerides (which may be
derived from either dietary fats or sugars) are said to
block leptin (a regulatory hormone) from reaching the brain.
Excessive fatty particles have also been implicated in cells
which are insulin resistant. A direct relationship has been
shown between excessive fructose consumption and elevated
triaglycerides. (low levels of frucose from whole fruit are
not a problem, and are probably advantageous).
IRS-1 and IRS-2 Insulin Receptor Substrates are proteins
involved in inducting glucose into cells for proper use
according to the cell's needs. There is evidence that IRS-2
may be compromised by excessive fructose. IRS-1 also
appears to be compromised by hyperglycemic 'osmotic
pressure'. I understand this to be excessive pressure
differences across cellular membranes caused by excessive
blood sugar. Hua Kul suggests that this condition requires
excessive BG possibly with high BF. The production of
insulin by pancreatic beta cells are understood to be under
the control of pathways via IRS-1.
**Coordination of Insulin Action and Secretion by IRS
Proteins** Morris F. White, Ph.D.
http://www.hhmi.org/research/investigators/white.html
There are far more knowledgeable people than me who read
smn. Contributions to correct my understanding most welcome.
Mike
Note: I am not diabetic, IR or obese, so what do I know?
Misc. excerpts from studies/articles referenced earlier.
"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.
**************
"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"
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.
*************
"Ever since I started reading about fructose and IRS-2 I
have been puzzled about the results of one study (1st one
below) that showed children singly deficient in either IRS-1
or IRS-2 did not become significantly insulin resistant, but
those deficient in both "showed a 25-35% decrease in
sensitivity." If fructose inhibits IRS-2 but not IRS-1, how
could it be the cause of such a huge increase in juvenile
obesity and diabetes? Then I discovered (thanks to poster
"kofi") the 2nd study posted below, which shows that an
increase in osmotic stress caused by hyperglycemia reduces
levels of IRS-1, "prolonged osmotic stress alters IRS-1
function by inducing its degradation, which could contribute
to the down-regulation of insulin action." Thus it would
appear that a combination diet of high fructose intake and
high carbohydrate intake (anything that raises blood glucose
levels significantly, which fructose does not do), would
reduce insulin sensitivity significantly. This is exactly a
large component of the typical teen diet, high carb snack
foods and high fructose soda. It might also indicate that
injections of IRS-1/IRS-2 could be an extremely powerful
weight reduction treatment, as well as a treatment for
symptoms of PCOS, but I don't know if these proteins are
available for medical use. from Hua Kul's post.
*************
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.
************
"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."
************
The researchers, led by Howard Hughes Medical Institute
investigator Gerald
I. Shulman, who is also professor of medicine and physiology
at Yale, published their findings in the February 12,
2004, issue of the New England Journal of Medicine.
"Prior to this work, it was pretty clear that insulin
resistance was the best predictor for the development of
type 2 diabetes; and that accumulation of lipid in muscle
correlated very strongly with insulin resistance," said
Shulman. This correlation has been observed in cross-
sectional studies, as well as in young people with a family
history of type 2 diabetes, he said.
"We found that these lean insulin-resistant offspring - who
have a high probability of later developing type 2 diabetes
- had muscle insulin resistance, but no detectable
abnormalities in their fat cells compared to the insulin-
sensitive subjects," said Shulman
************
Triglycerides block leptin from brain.
http://www.slu.edu/readstory/newsinfo/4263
************
"We now understand that IRS1 and IRS2 play unique roles in
mediating the effects of insulin and IGF1 on embryonic
development, postnatal somatic growth, and glucose
homeostasis: No embryos (16.5 days or older) lacking both
genes have been detected in our studies, suggesting that
signals coordinated by these IRS proteins are essential for
embryonic development. However, deletion of Irs1 alone
causes insulin resistance and growth retardation, but
diabetes never occurs."
"By contrast, mice without Irs2 grow into normal-size adults
that develop type 2 diabetes. Without IRS2, neonates are
insulin resistant but display appropriate compensatory
insulin secretion; as they age, however, the peripheral
insulin resistance is exacerbated by failure of the
pancreatic b cells." Morris F White.
