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Insulin pathway component explains insulin resistance, age-associated metabolic syndrome

La Jolla, Calif. -- Metabolic syndrome, an aging-associated group of disorders that includes insulin resistance, heart disease and high lipid levels, may be treatable thanks to a newly discovered role for a regulatory gene, according to a team of scientists at the Burnham Institute for Medical Research.

In addition, the scientists found that this single gene may contribute to the body's responses to caloric restriction and may explain some aspects of the Atkins Diet.

The gene's new function was discovered in Drosophila fruit flies; previously it was associated solely with the control of growth. Until now, how the gene regulates insulin, as well as other symptoms of metabolic syndrome, was largely unknown. The study was conducted by Sean Oldham, Ph.D., assistant professor, and his colleagues at the Burnham and the National Institute on Alcoholism and Alcohol Abuse. Oldham's findings appear in the journal Cell Metabolism to be released on August 8th.

Using fruit flies bred with a newly created mutant form of the gene TOR (short for target of rapamycin), Oldham and his colleagues were able to determine how the TOR pathway interacted with other important regulators of insulin, glucose and lipid metabolism.

TOR is an ancient gene, found in nearly all animal and plant cells. The researchers discovered that their new mutant fly reduced TOR function, allowing them to observe what happens when TOR's influence is removed.

Reductions in TOR function lowered glucose and lipid levels in the body. They also blocked the function of another important insulin regulator, a factor called FOXO, which is known to be a critical mediator of insulin signals and therefore glucose and lipid metabolism. In addition, flies with the mutated form of TOR had longer life spans than control flies.

"It has been unclear how TOR signaling affects the insulin pathway," said Oldham. "Our study adds another dimension to TOR's activity by revealing unexpe
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Contact: Nancy Beddingfield
nbeddingfield@burnham.org
858-646-3146
Burnham Institute
7-Aug-2006


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