1. Calpains play a role in insulin secretion and action.
- Author
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Sreenan, Seamus K., Yun-Ping Zhou, Otani, Kenichi, Hansen, Polly A., Currie, Kevin P.M., Chien-Yuan Pan, Jean-Pyo Lee, Ostrega, Diane M., Pugh, William, Horikawa, Yukio, Cox, Nancy J., Hanis, Craig L., Burant, Charles F., Fox, Aaron P., Bell, Graeme I., Polonsky, Kenneth S., Sreenan, S K, Zhou, Y P, Otani, K, and Hansen, P A
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CALPAIN ,INSULIN ,PHYSIOLOGY - Abstract
Studies of the genetic basis of type 2 diabetes suggest that variation in the calpain-10 gene affects susceptibility to this common disorder, raising the possibility that calpain-sensitive pathways may play a role in regulating insulin secretion and/or action. Calpains are ubiquitously expressed cysteine proteases that are thought to regulate a variety of normal cellular functions. Here, we report that short-term (4-h) exposure to the cell-permeable calpain inhibitors calpain inhibitor II and E-64-d increases the insulin secretory response to glucose in mouse pancreatic islets. This dose-dependent effect is observed at glucose concentrations above 8 mmol/l. This effect was also seen with other calpain inhibitors with different mechanisms of action but not with cathepsin inhibitors or other protease inhibitors. Enhancement of insulin secretion with short-term exposure to calpain inhibitors is not mediated by increased responses in intracellular Ca2+ or increased glucose metabolism in islets but by accelerated exocytosis of insulin granules. In muscle strips and adipocytes, exposure to both calpain inhibitor II and E-64-d reduced insulin-mediated glucose transport. Incorporation of glucose into glycogen in muscle also was reduced. These results are consistent with a role for calpains in the regulation of insulin secretion and insulin action. [ABSTRACT FROM AUTHOR]
- Published
- 2001
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