Arachidonic acid induced release of insulin and glucagon: role of endogenous prostaglandins in pancreatic hormone secretion.
The involvement of prostaglandins in the effects of arachidonic acid (20:4n-6) on insulin and glucagon release was investigated, using the isolated, perfused rat pancreas model. 20:4n-6, the substrate for dienoic prostaglandins, or 20:3n-3, a fatty acid that cannot be metabolized to prostaglandins were perfused over 55 min. 20: 4n-6 evoked triphasic insulin release: early and late phase during, and "off-response" following the perfusion. With 20:3n-3 the early phase of insulin release was 57% of that with 20:4n-6. 20:4n-6 stimulated only an early phase release of glucagon; 20:3n-3 had no effect. Indomethacin (10 microM, a cyclooxygenase inhibitor) inhibited by 50% the early phase of insulin and glucagon release induced by 20:4n-6, but did not modify insulin release during the early phase with 20:3n-3, or the late phase or off-response with either 20:4n-6 or 20:3n-3. We conclude that 1) the early phase release of insulin and glucagon which occurs with arachidonic acid is due in part to pancreatic biosynthesis of prostaglandins; and 2) in the other phases of insulin release evoked by the fatty acids, alternate "nonspecific" mechanisms may be involved.
D015126:8,11,14-Eicosatrienoic Acid / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D005934:Glucagon / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D010477:Perfusion; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D001095:Arachidonic Acids; D007328:Insulin; D011453:Prostaglandins; D016718:Arachidonic Acid; D005934:Glucagon; D015126:8,11,14-Eicosatrienoic Acid; D007213:Indomethacin