Interaction of Insulin and Prostacyclin Production in the Rat

The effects of hyperinsulinemia on production of prostacyclin (PGI₂), a potent inhibitor of platelet aggregation, was studied in vitro in the rat. Aortic rings following 1-h preincubation at 37°C and 1 h at 4°C were incubated with and without purified porcine insulin in Krebs' glucose at 37°C for 5 min and immediately percent inhibition of platelet aggregation was determined. PGI₂ production in ng/mg aorta was estimated from a curve using PGI₂ standard. The mean PGI₂ production was significantly decreased in those rings incubated with insulin in concentration of 2500, 500, and 250 microunits/ml. Likewise, incubation of rings at 22°C for 30 min resulted in at least ten times less PGI₂ with insulin. Since PGI₂ appears to exert its antiaggregatory effect through cyclic AMP, theophylline was added to the incubation medium resulting in potentiation of inhibition of aggregation which was decreased to control levels when insulin was also added to the medium. Pancreatic slices yielded no significant change in insulin obtained when incubated with and without 5 ng of PGI₂ in 2 ml of 2.8 mM glucose, but in a high glucose medium (28 mM) the PGI₂-treated slices yielded significantly less insulin. Since PGI₂ may play a role in the formation of atherosclerotic plaques, these results suggest a possible deleterious effect of elevated insulin levels in type II and in insulin-treated type I diabetics with regard to macrovascular disease. Suppression of insulin production in presence of PGI₂ in high glucose medium resembles the action of other prostaglandins and suggests it may inhibit insulin secretion after a glucose load.