Fatty acid incorporation into phospholipids of isolated pancreatic islets of the rat. Relationship to insulin release.
Fatty acid incorporation into specific phospholipids of isolated islets of the rat was investigated using unsaturated [14C]arachidonic acid. Glucose (25 mM) stimulated the incorporation of arachidonic acid into phosphatidylinositol (PI) and phosphatidylcholine (PC) in a time-related manner correlated with two phases of insulin release. Arachidonate incorporation was inhibited by calcium deprivation. The sulfonylurea tolbutamide stimulated an early monophasic release of insulin that was accompanied by increased [14C]arachidonate incorporation into PI and PC. The cholinergic agonist and insulin secretagogue, carbamylcholine, also promoted the incorporation of [14C]arachidonate into PI/phosphatidylserine (PS) and PC fractions. 2-Deoxy-D-glucose, which does not support insulin release, did not enhance arachidonate incorporation into phospholipids. However, phenylephrine, an inhibitor of glucose-induced insulin secretion, stimulated arachidonate turnover in PI. p-Bromophenacyl bromide, an inhibitor of phospholipase A2, markedly depressed both glucose-stimulated arachidonate incorporation into phospholipids and insulin release. The stimulated release of arachidonate from endogenous radiolabeled phospholipids provided additional evidence that phospholipase A2 mediates glucose stimulation. However, since glucose also promoted the incorporation of saturated [14C]palmitic acid into PE (phosphatidylethanolamine) and PI/PS fractions, a phospholipase A1 may also mediate the glucose response. Thus, fatty acid incorporation into islet phospholipids mediates the effects of various secretagogues on insulin release. However, the ability of phenylephrine to stimulate arachidonyl PI turnover suggests that fatty acid turnover is not a sufficient stimulus for release. Augmented levels of unsaturated fatty acids in islet cell membranes may promote fusion or activate enzymes important for hormone release.
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054466:Phospholipases A1; D054467:Phospholipases A2; D051381:Rats; D011919:Rats, Inbred Strains; D014044:Tolbutamide / Q000494:pharmacology
D001095:Arachidonic Acids; D007328:Insulin; D010713:Phosphatidylcholines; D010716:Phosphatidylinositols; D010656:Phenylephrine; D002217:Carbachol; D014044:Tolbutamide; D010741:Phospholipases A; D054466:Phospholipases A1; D054467:Phospholipases A2; D005947:Glucose