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[IP] Insulin Works in Brain, Affects Fertility

I got this on another diabetes list and found it fascinating, thought I
would forward it here.  Sorry if anyone already saw this but I know it
raises a lot of issues that many of us have had so thought it worth

 Insulin Works in Brain, Affects Fertility
 By Edward Edelson
 HealthSCOUT Reporter

 THURSDAY, Sept. 21 (HealthSCOUT) -- Insulin can act not only throughout the
 body but also in the brain, affecting appetite control, obesity and even
 reproductive fertility, two studies show.

 "Insulin has a previously unrecognized role in the brain," says Dr. C.
 Ronald Kahn, president of the Joslin Diabetes Center in Boston and leader
 a team reporting the finding in the journal Science. "We now have evidence
 that we need to look in much more detail about what is going on in the

 The Joslin researchers, working with scientists at the University of
 and the European Molecular Biology Laboratory in Germany, made their
 discovery by creating mice whose brain cells lack the receptors needed for
 insulin activity.

 "We found evidence of a decrease in the ability of insulin to lower blood
 glucose levels, increased appetite, obesity and increased infertility in
 genetically altered mice," Kahn says. "Our data show a central role of
 insulin resistance in regulating energy disposal, metabolism and

 The discovery could lead to treatments to help the estimated 16 million
 Americans with Type II diabetes, in which insulin production by the
 is reduced and tissues such as the muscles and liver show resistance to
 insulin, Kahn says: "In the next two years, studies could tell us what
 therapeutic interventions are possible."

 Decline in fertility a surprise

 The NIRKO (neural-insulin receptor knock out) mice created in the Joslin
 laboratory showed an expected obesity reaction to the loss of insulin
 function. The female mice gained weight on a normal diet, and both males
 females had weight gains ranging from 50 to 100 percent.

 The link to reproduction was more surprising. The NIRKO mice of both sexes
 had reduced fertility, an effect that was traced to defective regulation by
 the hypothalamus of leutinizing hormone, which affects both sperm
 and ovulation. That effect could help explain why some women with Type II
 diabetes who are overweight have menstrual disorders, with an increased
 incidence of polycystic ovary disease, the researchers say.

 A second study, appearing in the journal Nature, was done on mice bred to
 lack a different gene, one for insulin receptor substrate-2 (IRS-2), a
 protein found in many body cells. IRS-2 is essential for the normal
 of cells to insulin. In humans, Type II diabetes can occur when IRS-2
 activity is lessened, so that the pancreas cannot make enough insulin to
 meet the need of cells in the liver, muscle and fatty tissues.

 Male mice without IRS-2 die early, at 10 weeks of age. Female mice overeat,
 gain too much weight, have reduced fertility and develop diabetes between
 and 20 weeks of age. Their weight gain occurs even though the body produces
 excess amounts of leptin, a protein that suppresses appetite.

 That finding could change the textbook description of diabetes, which says
 that obesity is a risk factor for the disease, says Deborah J. Burks, lead
 author of the study and a research instructor at Joslin. Now it seems that
 it can work the other way around, with insulin resistance leading to

 "The studies provide very strong evidence that insulin is involved in the
 regulation of appetite, body weight and the reproductive process," Burks

 The reproductive problems of the female mice lacking IRS-2 begin early in
 life, when their ovaries develop fewer eggs. When the mice grow up and
 mature, they produce abnormally low amounts of gonadatropins, hormones that
 stimulate activity of the ovaries, and the ovaries are abnormally small and
 don't respond well to the hormones.

 So IRS-2 might be the source of many diabetes-related problems, says Morris
 F. White, another member of the Joslin research team. "You can live with
 reduced IRS-2 function, but you might be glucose intolerant, overeat and
 gain weight, have a difficult time becoming pregnant and when you do,
 develop gestational diabetes."

 What To Do

 These discoveries may someday change the way diabetes is defined and
 treated, but you should probably heed the current guidelines on preventing
 and managing the disease.

 By way of Leo Zaza, moderator email @ redacted

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