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Science 21 January 2005:
Vol. 307. no. 5708, pp. 380 - 384
DOI: 10.1126/science.1104345
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Type 2 Diabetes-a Matter of ß-Cell Life and Death?

Christopher J. Rhodes

In type 2 diabetes, the ß cells of the pancreas fail to produce enough insulin to meet the body's demand, in part because of an acquired decrease in ß-cell mass. In adults, pancreatic ß-cell mass is controlled by several mechanisms, including ß-cell replication, neogenesis, hypertrophy, and survival. Here, I discuss evidence supporting the notion that increased ß-cell apoptosis is an important factor contributing to ß-cell loss and the onset of type 2 diabetes. Interestingly, a key signaling molecule that promotes ß-cell growth and survival, insulin receptor substrate 2 (IRS-2), is a member of a family of proteins whose inhibition contributes to the development of insulin resistance in the liver and other insulin-responsive tissues. Thus, the IRS-2 pathway appears to be a crucial participant in the tenuous balance between effective pancreatic ß-cell mass and insulin resistance.

The Pacific Northwest Research Institute, 720 Broadway, Seattle, WA 98122, USA, and Department of Pharmacology, University of Washington, Seattle, WA 98122, USA.

E-mail: cjr{at}pnri.org

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