Interleukin 1-Induced Prostaglandin E2 Accumulation by Isolated Pancreatic Islets

  1. Michael L McDaniel
  1. Department of Pathology, Division of Laboratory Medicine, and Department of Internal Medicine, Washington University School of Medicine St. Louis, Missouri
  1. Address correspondence and reprint requests to Jonathan Hughes, Department of Pathology, Box 8118, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110.

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.

  • Received February 3, 1989.
  • Revision received June 14, 1989.
  • Accepted June 14, 1989.
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