Cellular Short Circuit Causes Insulin Resistance


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Future treatments for diabetes may correct the underlying causes of this prevalent metabolic disorder rather than just treat its symptoms. An important step in this direction has been made by Prof. Yehiel Zick of the Weizmann Institute's Molecular Cell Biology Department.

In a study reported in the November 21 issue of the Journal of Biological Chemistry, Zick and colleagues provided a new insight into the molecular basis of insulin resistance, a condition that can lead to diabetes. In insulin resistance, cells no longer respond to ordinary levels of insulin. The scientists discovered that this may occur because some of the proteins that relay messages from the insulin receptor to the glucose uptake machinery in cells undergo excessive phosphorylation (a process in which they acquire phosphorus atoms). Such abnormal phosphorylation generates a "short circuit" that prevents the insulin receptors from communicating their "messages" to the cells' interior, making the cells resistant to insulin.

In addition, the new study may explain why diabetes is five times more common in obese people than in people of normal weight. According to Prof. Zick, a major culprit in enhancing the inappropriate phosphorylation is a molecule called TNF, which is secreted by fat cells. The excessive secretion of TNF by obese people may explain the link between obesity, insulin resistance and diabetes.

These findings may in the future lead to new treatments for diabetes that would be based on correcting insulin resistance.

Prof. Zick's team included Ph.D. student Keren Paz, Dr. Eytan Elhanany of the Israel Institute for Biological Research, Dr. Hannah Kanety, Prof. Avraham Karasik, and Rina Hemi of the Sheba Medical Center in Tel Hashomer and Dr. Derek LeRoith of the National Institutes of Health, Bethesda, MD. This work was supported by research grants from the Kekst Foundation, the Israel Ministry of Health, the Tolz Foundation, the Israel Cancer Research Fund, the Israel Cancer Association, the Israel Science Foundation, and the Juvenile Diabetes Foundation International.

The Weizmann Institute of Science is a major center of scientific research and graduate study located in Rehovot, Israel.