One out of 12 people in the western world suffers from type 2 (adult onset) diabetes. Worldwide, 150 million people are diabetic and their numbers are expected to double in the next 20 years, a result of the growing obesity epidemic. Yet, the reasons for the strong correlation between excess body fat and diabetes have been puzzling researchers. Scientists at the Weizmann Institute of Science and the University of Umea, Sweden, have now unraveled a mechanism by which fat contributes to the onset of the disease. Their results were published in the April issue of Cell Metabolism.

Type 2 diabetes is a complex disease characterized by the body's inability to efficiently utilize sugar. Two stages of the disease have been identified: In the first, "silent" stage, the body's cells lose their ability to respond properly to the crucial hormone insulin, which is responsible for moving sugar from the blood into cells. If sugar remains in the bloodstream, the insulin-producing beta cells in the pancreas compensate by stepping up production. Eventually this leads to beta cell exhaustion, reduced insulin output and the appearance of full-blown diabetes.

Elevated fat in the bloodstream appears to accelerate both stages of the disease; but exactly how does this happen? The culprit may be a receptor known as GPR40 found on the outer surface of pancreatic beta cells. GPR40 was recently discovered to respond to fatty acids, alerting beta cells to their presence in the bloodstream. Beta cells were known to be attuned to changes in blood glucose levels, responding to after-meal glucose surges with a sharp increase in insulin production. But when fat is present in addition to sugar, the GPR40 receptor causes even greater insulin output. Frequent overstimulation of the beta cells may be tied to persistently elevated insulin levels, hastening the onset of the disease.

How does this destructive cycle begin? To understand GPR40's role, Prof. Michael Walker and students
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Contact: Alex Smith
asmith@jgordonassociates.com
212-367-3892
American Committee for the Weizmann Institute of Science
16-May-2005

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