Diabetes, Vol 38, Issue 10 1251-1257, Copyright © 1989 by American Diabetes Association

ARTICLES

Interleukin 1-induced prostaglandin E2 accumulation by isolated pancreatic islets

JH Hughes, RA Easom, BA Wolf, J Turk and ML McDaniel
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.

Recombinant human interleukin 1 alpha (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 glucose-induced insulin secretion and islet glucose oxidation. Maximal stimulation of PGE2 accumulation (5 times control value) occurred at 200 pM IL-1, and half-maximal 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 microM indomethacin did not influence the inhibitory effects of IL-1 on glucose-induced 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.
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