Inhibition of in vivo insulin secretion by prostaglandin E1

To determine the effect of prostaglandin E(1) (PGE(1)) infusion upon in vivo insulin secretion, serum insulin responses after an intravenous glucose pulse (2 g) were measured before and during an intravenous infusion of PGE(1) (10 mug/min) in 11 anesthetized dogs. Circulating insulin decreased significantly during PGE(1) infusion were significantly less than control responses. Three dogs received PGE(1) infusions into the thoracic aorta to preclude pulmonic and hepatic degradation of PGE(1) before its arrival at the pancreatic artery; inhibition of insulin secretion was again seen. Inhibition of insulin secretion could not be related to the degree of arterial hypotension induced by intravenous PGE(1), and despite alpha adrenergic blockade with intravenous phentolamine, PGE(1)-induced inhibition of glucose-stimulated insulin responses persisted. Significant increments in systemically circulating PGE levels during intravenous PGE(1) infusions were documented by radioimmunoassay. These studies demonstrate that systemic PGE(1) infusion inhibits insulin secretion and that this effect could not be shown to be dependent upon alpha adrenergic activity.