BOSTON -- A study led by researchers at Beth Israel Deaconess Medical Center (BIDMC) has shown that a protein found in fat cells is a newly discovered cause of insulin resistance, establishing a previously unidentified molecular link between obesity and type 2 diabetes and offering a potential new target for the development of drugs to treat diabetes. The findings appear in the July 21, 2005, issue of the journal Nature.

According to senior author Barbara B. Kahn, MD, Chief of the Division of Endocrinology, Diabetes, and Metabolism at BIDMC, these findings in both mice and humans represent the first evidence that elevated levels of retinol binding protein 4 (RBP4) play a key role in the development of insulin resistance, a primary risk factor for diabetes.

"Being resistant to insulin is one of the major causes of diabetes," says Kahn, who is also a Professor of Medicine at Harvard Medical School. "And even in the absence of diabetes, insulin resistance is a major risk factor for heart disease and early mortality."

Produced by the pancreas, the hormone insulin functions to help cells throughout the body take in glucose and convert the simple sugar to energy. In individuals who are resistant to insulin, the body's muscle, fat and liver cells are unable to properly respond to the hormone, resulting in a build-up of glucose and insulin in the blood which, in turn, can lead to the development of diabetes and cardiovascular disease.

Earlier work in Kahn's lab had focused on understanding the role of a glucose transporter protein called GLUT4 in the development of insulin resistance. Knowing that downregulation of GLUT4 expression in fat tissue is an almost universal feature of insulin-resistant states (including obesity, type 2 diabetes and the metabolic syndrome), previous members of Kahn's lab developed two transgenic mouse models: One with fat-cell specific overexpression of GLUT4 and one with fat-cell specific reduction of GLU
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Contact: Bonnie Prescott
bprescot@bidmc.harvard.edu
617-667-7306
Beth Israel Deaconess Medical Center
20-Jul-2005

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