Prostaglandins and the release of insulin. A review and a proposal

The effect of prostaglandins or the inhibition of their synthesis on the release of insulin is controversial. Dispute exists because there are apparently disparate experimental results. When the following factors are considered, however, much of the disparity is eliminated: 1) the experimental setting--in vitro or in vivo; 2) the experimental model--animal or human; 3) the experimental additive--the type of nonsteroidal antiinflammatory drug or specific prostaglandin; 4) the relationship of insulin levels to insulin secretion, degradation, and the observed hypoglycemic response. On the basis of such considerations the following conclusions are advanced. 1) From animal studies in vitro it appears that prostaglandins can directly augment insulin release. 2) Results from animal experiments in vivo, however, suggest that systemic prostaglandin administration diminishes insulin release. 3) No human studies have been performed in vitro which examine the insulin secretory response of pancreatic tissue to prostaglandins. 4) Prostaglandins reduce stimulated insulin levels in normal human subjects and in those with diabetes mellitus. Whether insulin secretion is reduced, or clearance is increased, is unknown. 5) Finally, the critical experiment remains to be done, that is the simultaneous examination of insulin, C-peptide, and glucose kinetics during an infusion of a prostaglandin.