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Powerful antibody-based strategy suggests a new therapeutic approach to diabetes and obesity
Date:9/29/2011

Cold Spring Harbor, NY The work of a team of scientists at Cold Spring Harbor Laboratory (CSHL) led by Professor Nicholas Tonks FRS, suggests a way to overcome one of the major technical obstacles preventing a leading therapeutic target for diabetes and obesity from being addressed successfully by novel drugs.

The target is an enzyme called PTP1B, discovered by Tonks in 1988 and long known to be an important player in the signaling pathway within cells that regulates the response to insulin. Insulin is a hormone that regulates carbohydrate and fat metabolism by spurring cells, particularly in the liver and muscle, to absorb glucose from the bloodstream and store it away for later use.

Insulin exerts its effects by binding to a receptor on the surface of a cell. This receptor then triggers a signaling cascade that involves sequential chemical reactions in which phosphate is added to target proteins by enzymes called kinases. In fact, the insulin receptor is itself a kinase that phosphorylates target proteins on specific tyrosine residues. Phosphorylation of this amino acid in target proteins serves as a switch to regulate function, thereby transmitting the effects of insulin to the machinery of the cell. The effects of the insulin receptor are countered by members of a family of enzymes called the protein tyrosine phosphatases (PTPs), which take the phosphate group back off tyrosine residues in proteins. Of particular importance to the regulation of insulin signaling is the phosphatase PTP1B.

"Type 2 Diabetes, the most common form, is a disease of insulin resistance," Tonks explains. "In the disease state, an insulin molecule docks at a cell, but the cellular mechanism that sends its signal does not work properly. This is why simply adding more insulin will not solve the problem. What you really need to do is to promote insulin signaling within the cell to favor the phosphorylation events triggered by the insulin receptor."


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Contact: Peter Tarr
tarr@cshl.edu
516-367-8455
Cold Spring Harbor Laboratory
Source:Eurekalert

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