Inhibition of in vivo insulin secretion by prostaglandin E₁

To determine the effect of prostaglandin E₁ (PGE₁) 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 PGE₁ (10 μg/min) in 11 anesthetized dogs. Circulating insulin decreased significantly during PGE₁ infusion, and insulin responses after glucose during PGE₁ infusion were significantly less than control responses. Three dogs received PGE₁ infusions into the thoracic aorta to preclude pulmonic and hepatic degradation of PGE₁ 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 PGE₁, and despite alpha adrenergic blockade with intravenous phentolamine, PGE₁ induced inhibition of glucose stimulated insulin responses persisted. Significant increments in systemically circulating PGE levels during intravenous PGE₁ infusions were documented by radioimmunoassay. These studies demonstrate that systemic PGE₁ infusion inhibits insulin secretion and that this effect could not be shown to be dependent upon alpha adrenergic activity. (16 references.)