{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T22:19:10Z","timestamp":1758925150222},"reference-count":0,"publisher":"American Diabetes Association","issue":"8","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1997,8,1]]},"abstract":"<jats:p>A number of agents that inhibit oxidative phosphorylation by different mechanisms (carbonyl cyanide m-chlorophenylhydrazone [CCCP], sodium azide, oligomycin) induced an increase of cytoplasmic Ca2+ concentration ([Ca2+]i) in pancreatic \u03b2-cells, as measured by microfluorimetry with digital imaging. All three agents are known inhibitors of insulin secretion, and the secretory response to 20 mmol\/l glucose was found to be abolished in spite of elevated [Ca2+]i. Two reasons could account for this dissociation between increase of [Ca2+]i and insulin secretion: 1) the increase did not take place at a site critical for exocytosis, 2) a threshold concentration of a metabolism-derived factor like ATP exists for the induction of exocytosis. The increase of [Ca2+]i by CCCP and sodium azide involved release of Ca2+ from internal stores, whereas oligomycin induced a slow D 600\u2013inhibitable Ca2+ influx. Because CCCP and sodium azide, but not oligomycin, decreased the mitochondrial membrane potential concomitantly with the increase of [Ca2+]i, release of Ca2+ from the mitochondria most probably plays a decisive role for the internal mobilization. A Ca2+ influx induced by 40 mmol\/l K+ or 250 \u03bcmol\/l tolbutamide was unimpaired in the presence of oligomycin, but oligomycin completely abolished insulin secretion in response to these agents. While CCCP and sodium azide opened ATP-sensitive K+ channels, oligomycin was virtually ineffective, although it could be shown to significantly reduce \u03b2-cell ATP production. By comparison of the effects of different inhibitors of oxidative phosphorylation, we conclude that the initiation of exocytosis in \u03b2-cells is particularly sensitive to a decrease of energy metabolism, more than ATP-sensitive K+ channels or voltage-dependent Ca2+ channels. Thus, any increase of [Ca2+]i in \u03b2-cells that occurs in a situation of a decreased ATP supply is unlikely to elicit a secretory response.<\/jats:p>","DOI":"10.2337\/diab.46.8.1305","type":"journal-article","created":{"date-parts":[[2013,9,19]],"date-time":"2013-09-19T17:42:54Z","timestamp":1379612574000},"page":"1305-1311","update-policy":"http:\/\/dx.doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":24,"title":["Energetic Requirement of Insulin Secretion Distal to Calcium Influx"],"prefix":"10.2337","volume":"46","author":[{"given":"Ingo","family":"Rustenbeck","sequence":"first","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of G\u00f6ttingen,\u2008G\u00f6ttingen, Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cornelia","family":"Herrmann","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of G\u00f6ttingen,\u2008G\u00f6ttingen, Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Grimmsmann","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of G\u00f6ttingen,\u2008G\u00f6ttingen, Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","container-title":["Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.org\/diabetes\/diabetes\/article-pdf\/46\/8\/1305\/362640\/46-8-1305.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/46\/8\/1305\/362640\/46-8-1305.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T16:34:01Z","timestamp":1667406841000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/46\/8\/1305\/9227\/Energetic-Requirement-of-Insulin-Secretion-Distal"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,8,1]]},"references-count":0,"journal-issue":{"issue":"8","published-print":{"date-parts":[[1997,8,1]]}},"URL":"https:\/\/doi.org\/10.2337\/diab.46.8.1305","relation":{},"ISSN":["0012-1797","1939-327X"],"issn-type":[{"value":"0012-1797","type":"print"},{"value":"1939-327X","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,8,1]]}}}