Endogenous prostaglandin synthesis and glucose-induced insulin secretion from the adult rat pancreatic islet.

Although exogenous prostaglandins are recognized modulators of insulin secretion, the relationship between their endogenous synthesis and insulin secretion has not been rigorously studied in isolated adult rat islets. Using 3H-arachidonic acid as a tracer, we evaluated the effect of glucose stimulation upon the incorporation of this fatty acid into islet phospholipids and prostaglandins (separated by extraction and sequential silicic acid, thin-layer and paper chromatography). We observed that 3H-arachidonic acid was incorporated into islet phospholipids and prostaglandins under basal conditions (0.3 mg/ml glucose). Furthermore, exposure of islets to a stimulatory glucose concentration led to significant increases in the recovery of 3H-arachidonic acid-derived radioactivity in islet phosphatidylethanolamine, phosphatidylserine, sphingomyelin, and phosphatidylinositol as well as into all of the measured prostaglandins (A2, B2, D2, E2, and F2 alpha). The most marked increases in recovered radioactivity resulting from a stimulatory glucose concentration were in islet phosphatidylethanolamine and prostaglandin A2 (which we believe to be derived, in large part, from endogenously synthesized prostaglandin E2). These glucose-induced increases in 3H-arachidonic acid-derived radioactivity in both the phospholipid and the prostaglandin fractions were eliminated by the inhibition of phospholipase A2 activity with mepacrine or by the inhibition of cyclooxygenase activity with sodium salicylate. When islets prelabeled with 3H-arachidonic acid were exposed to a high glucose concentration in a perifusion system, there was a brisk extracellular release of radioactivity (presumably representing unidentified prostaglandins) that began within 1 min and that peaked slightly before the peak of the first phase of insulin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)