The effect of flurbiprofen, a potent inhibitor of prostaglandin synthesis, on insulin and glucagon release from isolated rat pancreas.
The influence of different levels of inhibition of prostaglandin (PG) synthesis on the release of insulin and glucagon was investigated in the basal state (5.6 mM glucose) and in response to 30-min perfusion of 16.7 mM glucose using the isolated perfused rat pancreas model. Flurbiprofen (FLR), a potent and selective inhibitor of PG synthesis, was present in the perfusate during the entire experimental period at a concentration of 10(-8), 5 X 10(-8), or 10(-6) M; control experiments were performed without the drug. Levels of immunoreactive PGE2, PGF2 alpha, insulin, and glucagon were measured in the portal venous effluent. FLR inhibited PG synthesis in a dose-related manner; PGE2 was inhibited more than PGF2 alpha. Basal and glucose-induced secretion of insulin was augmented by FLR at 5 X 10(-8) M, but was inhibited at 10(-6) M. At 10(-6) M FLR, basal glucagon secretion was inhibited; glucose-induced suppression still occurred without any potentiation. We conclude that 1) endogenous PGs modulate the secretion of insulin and glucagon; 2) divergence of the effects of low and high levels of inhibition of PG biosynthesis on insulin release may be due to altered tissue proportions of various PGs and related autacoids; and 3) the predominant effect of endogenous PGs on glucagon release is tonic stimulation.
D000818:Animals; D015237:Dinoprost; D015232:Dinoprostone; D005480:Flurbiprofen / Q000494:pharmacology*; D005934:Glucagon / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D011422:Propionates / Q000494:pharmacology*; D011448:Prostaglandin Antagonists; D011458:Prostaglandins E / Q000378:metabolism; D011460:Prostaglandins F / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D007328:Insulin; D011422:Propionates; D011448:Prostaglandin Antagonists; D011458:Prostaglandins E; D011460:Prostaglandins F; D005480:Flurbiprofen; D005934:Glucagon; D015237:Dinoprost; D015232:Dinoprostone