{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T22:47:07Z","timestamp":1771627627095,"version":"3.50.1"},"reference-count":0,"publisher":"American Diabetes Association","issue":"11","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1988,11,1]]},"abstract":"<jats:p>A number of indirect studies suggest a role for endogenous arachidonic acid (AA) in pancreatic islet function. To probe the effects of this fatty acid, AA and other polyunsaturated fatty acids were exogenously provided in Ca2+-free medium to avoid the formation of insoluble or impermeant Ca2+-arachidonate complexes. Concentrations of AA of \u22673 \u03bcM induced potent and sustained but reversible 45Ca efflux from prelabeled intact (or digitonin-permeabilized) islets; AA also nduced insulin release at somewhat higher concentrations. Other unsaturated fatty acids (erucic, oleic, linoleic, linolenic, dihomo-\u03b3-linolenic, eicosapentaenoic, docosahexaenoic acids) were generally less active than AA itself, indicating a structure-function relationship. The effects of AA were saturable, were inhibitable by cooling, and were not accompanied in parallel by 51Cr release or trypan blue retention, suggesting a nontoxic mechanism. At low concentrations (3.3\u201316 \u03bcM), at which AA does not stimulate insulin release, AA-induced 45Ca efflux was not reduced by pretreatment with ionomycin (to deplete membrane-bound Ca2+ stores), suggesting stimulation of Ca2+ extrusion through the plasma membrane. At higher concentrations (\u226725 \u03bcM), at which AA promotes insulin release, further Ca2+ efflux was stimulated, which was blunted by pretreatment with ionomycin (as well as by trifluoperazine). Conversely, pretreatment with AA obliterated the effects of ionomycin (3 \u03bcM) on cellular Ca2+ mobilization. Thus, AA also mobilizes Ca2+ from intracellular organelles, leading to a rise in free cytosolic Ca2+ (as previously reported). AA-induced 45Ca efflux and insulin release were independent of the presence of extracellular Na+ and did not require the oxygenation of AA. Dose-response curves comparing45Ca efflux and insulin secretion suggested that AA also stimulates hormone release by at least one other mechanism in addition to Ca2+ mobilization. This second stimulatory effect of AA could be seen in digitonin-permeabilized islets, where changes in cytosolic free Ca2+ concentration were vitiated by EGTA-containing buffers. Such secretion was also saturable and was inhibited by cooling or by spermine (which inhibits protein kinase C in the islet). Furthermore, AA-induced secretion from either intact or permeabilized islets was blunted by prolonged pretreatment of islets with a phorbol ester to deplete them of protein kinase C. Thus, exogenous arachidonic acid seems to be a complete secretagogue, having stimulatory effects both on Ca2+ mobilization and Ca2+-related secretory processes, putatively the activation of protein kinase C.<\/jats:p>","DOI":"10.2337\/diab.37.11.1453","type":"journal-article","created":{"date-parts":[[2013,9,19]],"date-time":"2013-09-19T17:16:02Z","timestamp":1379610962000},"page":"1453-1469","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":50,"title":["Exogenous Arachidonic Acid Promotes Insulin Release From Intact or Permeabilized Rat Islets by Dual Mechanisms: Putative Activation of Ca2+ Mobilization and Protein Kinase C"],"prefix":"10.2337","volume":"37","author":[{"given":"Stewart A","family":"Metz","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Colorado Health Sciences Center, and the Research Service, Denver Veterans Administration Medical Center\u2008Denver, Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","container-title":["Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.org\/diabetes\/diabetes\/article-pdf\/37\/11\/1453\/355495\/37-11-1453.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/37\/11\/1453\/355495\/37-11-1453.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T16:08:16Z","timestamp":1667405296000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/37\/11\/1453\/8136\/Exogenous-Arachidonic-Acid-Promotes-Insulin"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1988,11,1]]},"references-count":0,"journal-issue":{"issue":"11","published-print":{"date-parts":[[1988,11,1]]}},"URL":"https:\/\/doi.org\/10.2337\/diab.37.11.1453","relation":{},"ISSN":["0012-1797","1939-327X"],"issn-type":[{"value":"0012-1797","type":"print"},{"value":"1939-327X","type":"electronic"}],"subject":[],"published":{"date-parts":[[1988,11,1]]}}}