Calpains play a role in insulin secretion and action.

Sreenan SK, Zhou YP, Otani K, Hansen PA, Currie KP, Pan CY, Lee JP, Ostrega DM, Pugh W, Horikawa Y, Cox NJ, Hanis CL, Burant CF, Fox AP, Bell GI, Polonsky KS
Diabetes. 2001 50 (9): 2013-20

PMID: 11522666 · DOI:10.2337/diabetes.50.9.2013

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.

MeSH Terms (21)

Adipocytes Animals Calcium Calpain Cysteine Proteinase Inhibitors Deoxyglucose Electric Conductivity Glucose Insulin Insulin Secretion Intracellular Membranes In Vitro Techniques Islets of Langerhans Leucine Mice Mice, Inbred C57BL Muscle, Skeletal NADP Oligopeptides Osmolar Concentration Time Factors

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