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- Title
Calpains play a role in insulin secretion and action.
- Authors
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; Hansen, P A
- 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.
- Subjects
CALPAIN; INSULIN; PHYSIOLOGY
- Publication
Diabetes, 2001, Vol 50, Issue 9, p2013
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/diabetes.50.9.2013