Interleukin 1-induced prostaglandin E2 accumulation by isolated pancreatic islets.
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.
Hughes
J H
JH
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.
Easom
R A
RA
Wolf
B A
BA
Turk
J
J
McDaniel
M L
ML
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis*; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006019:Glycolysis / Q000187:drug effects; D007052:Ibuprofen / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology
D001095:Arachidonic Acids; D007328:Insulin; D007375:Interleukin-1; D011994:Recombinant Proteins; D016718:Arachidonic Acid; D005947:Glucose; D015232:Dinoprostone; D007052:Ibuprofen; D007213:Indomethacin