{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T13:42:05Z","timestamp":1791034925653,"version":"4.1.0"},"reference-count":22,"publisher":"American Diabetes Association","issue":"9","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,9,1]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.2337\/diabetes.50.9.2013","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T19:04:22Z","timestamp":1173207862000},"page":"2013-2020","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":138,"title":["Calpains Play a Role in Insulin Secretion and Action"],"prefix":"10.2337","volume":"50","author":[{"given":"Seamus K.","family":"Sreenan","sequence":"first","affiliation":[{"name":"Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Ping","family":"Zhou","sequence":"additional","affiliation":[{"name":"Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Otani","sequence":"additional","affiliation":[{"name":"Medicine"},{"name":"Department of Medicine, Washington University, St. Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Polly A.","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Parke-Davis Pharmaceutical Research Division\/Warner-Lambert Company, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin P.M.","family":"Currie","sequence":"additional","affiliation":[{"name":"Neurobiology, Pharmacology and Physiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Yuan","family":"Pan","sequence":"additional","affiliation":[{"name":"Neurobiology, Pharmacology and Physiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Pyo","family":"Lee","sequence":"additional","affiliation":[{"name":"Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane M.","family":"Ostrega","sequence":"additional","affiliation":[{"name":"Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Pugh","sequence":"additional","affiliation":[{"name":"Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukio","family":"Horikawa","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology, and"},{"name":"Howard Hughes Medical Institute, the University of Chicago, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy J.","family":"Cox","sequence":"additional","affiliation":[{"name":"Medicine"},{"name":"Human Genetics, and the"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig L.","family":"Hanis","sequence":"additional","affiliation":[{"name":"Human Genetics Center, the University of Texas Health Science Center at Houston, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles F.","family":"Burant","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Parke-Davis Pharmaceutical Research Division\/Warner-Lambert Company, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron P.","family":"Fox","sequence":"additional","affiliation":[{"name":"Neurobiology, Pharmacology and Physiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graeme I.","family":"Bell","sequence":"additional","affiliation":[{"name":"Medicine"},{"name":"Biochemistry and Molecular Biology, and"},{"name":"Human Genetics, and the"},{"name":"Howard Hughes Medical Institute, the University of Chicago, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth S.","family":"Polonsky","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University, St. Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031207055618500_R1","unstructured":"DeFronzo RA: Pathogenesis of type 2 diabetes: metabolic and molecular implications for identifying diabetes genes. 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