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The battle for CRTC2: How obesity increases the risk for diabetes
Date:6/21/2009

La Jolla, CAObesity is probably the most important factor in the development of insulin resistance, but science's understanding of the chain of events is still spotty. Now, researchers at the Salk Institute for Biological Studies have filled in the gap and identified the missing link between the two. Their findings, to be published in the June 21, 2009 advance online edition of the journal Nature, explain how obesity sets the stage for diabetes and why thin people can become insulin-resistant.

The Salk team, led by Marc Montminy, Ph.D., a professor in the Clayton Foundation Laboratories for Peptide Biology, discovered how a condition known as ER (endoplasmic reticulum) stress, which is induced by a high fat diet and is overly activated in obese people, triggers aberrant glucose production in the liver, an important step on the path to insulin resistance.

In healthy people, a "fasting switch" only flips on glucose production when blood glucose levels run low during fasting. "The existence of a second cellular signaling cascadelike an alternate route from A to Bthat can modulate glucose production, presents the potential to identify new classes of drugs that might help to lower blood sugar by disrupting this alternative pathway," says Montminy.

It had been well established that obesity promotes insulin resistance through the inappropriate inactivation of a process called gluconeogenesis, where the liver creates glucose for fuel and which ordinarily occurs only in times of fasting. Yet, not all obese people become insulin resistant, and insulin resistance occurs in non-obese individuals, leading Montminy and his colleagues to suspect that fasting-induced glucose production was only half the story.

"When a cell starts to sense stress a red light goes on, which slows down the production of proteins," explains Montminy. "This process, which is known as ER stress response, is abnormally active in livers of obese individua
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Contact: Gina Kirchweger
Kirchweger@salk.edu
858-453-410-01340
Salk Institute
Source:Eurekalert  

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