Abstract

Recombinant human interleukin 1α (IL-1) has been found to induce prostaglandin E₂ (PGE₂) accumulation by isolated rat islets of Langerhans at concentrations similar to those at which the cytokine inhibits glucoseinduced insulin secretion and islet glucose oxidation. Maximal stimulation of PGE₂ accumulation (5 times control value) occurred at 200 pM IL-1, and halfmaximal stimulation occurred at 25 pM IL-1. Significant augmentation of PGE₂ accumulation by IL-1 required 10–18 h of exposure to the cytokine. Islets that had been pretreated with IL-1 for 18 h showed elevated rates of PGE₂ production at basal (3-mM) and stimulatory (16.5-mM) glucose concentrations and converted exogenous arachidonic acid to PGE₂ at twice the maximal rate of control islets. Exogenous PGE₂ did not mimic the inhibitory effects of IL-1 on glucose-induced insulin secretion or glucose oxidation. To rule out the possibility that endogenous PGE₂ is involved in the inhibitory effects of IL-1, the effect of a cyclooxygenase inhibitor on IL-1-treated islets was examined. Pharmacological blockade of PGE₂ biosynthesis by 10 JAM indomethacin did not influence the inhibitory effects of IL-1 on glucoseinduced insulin secretion or glucose oxidation. Thus, exogenous PGE₂ does not mimic the effects of IL-1 on islets, and inhibition of endogenous PGE₂ biosynthesis does not suppress the effects of IL-1 on islets. These results suggest that PGE₂ is not a principal mediator of the inhibitory effects of IL-1 on glucose-induced insulin secretion or glucose oxidation.