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 j.v. glucose, 5 g i.v. arginine, and 1 mg i.v. glucagon before and one hour after ingestSbn 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 μU/ml, 
± SE, p < 0.02, paired t-test) while placebo failed to alter basal insulin (pre, 8 ± 2.7; post, 6.9 ± 0.6 μU/ml). INDO substantially blunted the AIR to 5 g glucose (Δ3–5' IRI pre, 20.3 ± 3; post, 8.4 ± 2.4 μU/ml, P < 0.005), 20 g glucose (Δ3–5' IRI pre, 38.1 ± 9.7; post, 18.9 ± 8 μU/ml, P < 0.005), and 1 mg glucagon (0–10' IRI area pre, 375 ± 73; post, 149 ± 30 μU · min/ml, P < 0.05), but it failed to influence arginine-stimulated AIR (0–10' IRI area pre, 161 ± 34; post, 186 ± 31). Thus, PG inhibition with INDO lowers basal, glucose-, and glucagon-stimulated AIR, but it has ho effect on arginine-stimulated AIR. Our data suggest that endogenous PGs enhance insulin secretion.
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