PMID: 6769727May 1, 1980Paper

Effects of indomethacin on acute insulin release in man

E Topol, R G Brodows


Prostaglandin (PG) E2 stimulates glucose-induced insulin release from isolated rat pancreatic islets but inhibits acute insulin release to intravenous (i.v.) glucose in man. Since PGs act as intracellular messengers, we have studied the effect of endogenous PG inhibition with indomethacin (a potent PG synthesis inhibitor) to clarify these differences. The acute insulin response (AIR) to 5 g and 20 g i.v. glucose, 5 i.v. arginine, and 1 mg i.v. glucagon before and one hour after ingestion of 50 mg indomethacin (INDO) or placebo was studied in healthy lean subjects. INDO significantly lowered basal insulin levels (pre, 9.5 +/- 1.6; post, 6.4 +/- 1.8 muU/ml, X +/- SE, p less than 0.02, paired t-test) while placebo failed to alter basal insulin (pre, 8 +/- 2.7; post, 6.9 +/- 0.6 muU/ml). INDO substantially blunted the AIR to 5 g glucose (delta3-5' IRI pre,20.3 +/- 3; post, 8.4 +/- 2.4 muU/ml, p less than 0.005), 20 g glucose (delta3-5' IRI pre, 38.1 +/- 9.7; post, 18.9 +/- 8 muU/ml, p less than 0.005), and 1 mg glucagon (0-10' IRI area pre, 375 +/- 73; post, 149 +/- 30 muU . min/ml, p less than 0.05), but it failed to influence agrinine-stimulated AIR (0-10' IRI area pre, 161 +/- 34; post, 186 +/- 31). Thus, PG inhibition with INDO...Continue Reading


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