Corn syrup linked to diabetes

please don't cross post


On Sat, 15 May 2004 04:26:48 GMT, "Mike V"
wrote:


"Hua Kul" wrote in message
. com...
"Mike V" wrote in message
rthlink.net...
"Hannah Gruen" wrote in message
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"Diarmid Logan" wrote in message
om...
http://www.nature.com/nsu/040510/040510-5.html

Corn syrup linked to diabetes


Big Snip


Thank you all for posting and reposting this information. I would
like to add a little bit more that I have discovered. 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.

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Diabetes. 2002 Dec;51 Suppl 3:S304-7.

Increased insulin resistance in obese children who have both 972 IRS-1
and 1057 IRS-2 polymorphisms.
Le Fur S, Le Stunff C, Bougneres P.
Department of Pediatric Endocrinology, Hopital Saint-Vincent de Paul,
Universite Paris V, Paris, France.

In two cohorts of 174 and 165 obese Caucasian children, we measured
insulin sensitivity and genotyped insulin receptor substrate IRS-1 and
IRS-2 genes for the Arg972Gly and the Asp1057Gly variants,
respectively. Because IRS-1 and IRS-2 have complementary roles in
insulin signaling, we classified the genotypes in three categories:
those with none of the variants in IRS-1 or IRS-2, those with one
variant in IRS-1 or IRS-2, and those with variants in both IRS-1 and 2
proteins. The obese children with either the IRS-1 or IRS-2 variant
had a mean insulin sensitivity index (2.9 +/- 0.2 in cohort 1, 2.7 +/-
0.1 in cohort 2) only slightly lower than the children having no
variant in either gene (3.1 +/- 0.2 and 3.5 +/- 0.3, respectively).
However, patients having variant alleles in both IRS-1 and IRS-2 genes
showed a 25-35% decrease in sensitivity (2.3 +/- 0.2 and 2.0 +/- 0.2,
respectively) when compared with nonvariant homozygotes (P 0.001).
These observations are reminiscent of the insulin sensitivity
phenotypes in double IRS-1(+/-) IRS-2(+/-) heterozygous knockout mice.
Our results stress the need for combined genotype analysis when
candidate genes are functionally involved in the same pathway.

PMID: 12475767 [PubMed - indexed for MEDLINE]
================================================== =====================

================================================== =====================
J Biol Chem. 2003 Jul 18;278(29):26550-7. Epub 2003 May 01.

Hyperosmotic stress inhibits insulin receptor substrate-1 function by
distinct mechanisms in 3T3-L1 adipocytes.
Gual P, Gonzalez T, Gremeaux T, Barres R, Le Marchand-Brustel Y, Tanti
JF.
INSERM U 568 and l'Institut Federatif de Recherches 50, Faculte de
Medecine, Avenue de Valombrose, 06107 Nice Cedex 02, France.

In 3T3-L1 adipocytes, hyperosmotic stress was found to inhibit insulin
signaling, leading to an insulin-resistant state. We show here that,
despite normal activation of insulin receptor, hyperosmotic stress
inhibits both tyrosine phosphorylation of insulin receptor substrate-1
(IRS-1) and IRS-1-associated phosphoinositide 3 (PI 3)-kinase activity
in response to physiological insulin concentrations. Insulin-induced
membrane ruffling, which is dependent on PI 3-kinase activation, was
also markedly reduced. These inhibitory effects were associated with
an increase in IRS-1 Ser307 phosphorylation. Furthermore, the
mammalian target of rapamycin (mTOR) inhibitor rapamycin prevented the
osmotic shock-induced phosphorylation of IRS-1 on Ser307. The
inhibition of mTOR completely reversed the inhibitory effect of
hyperosmotic stress on insulin-induced IRS-1 tyrosine phosphorylation
and PI 3-kinase activation. In addition, prolonged osmotic stress
enhanced the degradation of IRS proteins through a
rapamycin-insensitive pathway and a proteasome-independent process.
These data support evidence of new mechanisms involved in osmotic
stress-induced cellular insulin resistance. Short-term osmotic stress
induces the phosphorylation of IRS-1 on Ser307 by an mTOR-dependent
pathway. This, in turn, leads to a decrease in early proximal
signaling events induced by physiological insulin concentrations. On
the other hand, prolonged osmotic stress alters IRS-1 function by
inducing its degradation, which could contribute to the
down-regulation of insulin action.

PMID: 12730242 [PubMed - indexed for MEDLINE]
================================================== ===============

--Hua Kul


Thanks for putting it all together Hua. It takes a lot of concentration to
parse and reassemble relevant bits of news.
Sometime I wonder if the researchers focus too narrowly, and often miss such
relationships.
How do you think insulin mimetics such as cinnamon/mhcp fit in with this?

MikeV