A Role for Prostaglandin E in Defective Insulin Secretion and Carbohydrate Intolerance in Diabetes Mellitus

Prostaglandin E₂ (PGE₂) infusion in normal humans inhibited acute insulin responses to a glucose (5 g i.v.) pulse (response before PGE₂ = 593 ± 104%; during PGE₂ = 312±55%; mean±SE, mean change 3-5 min insulin,% basal, P < 0.005). This effect was associated with a decrease in glucose disappearance rates (K_G before PGE₂ = 0.73±0.07; during PGE₂ = 0.49±0.06%/min, P < 0.025). Acute insulin responses to arginine (2 g i.v.) were not affected by PGE₂ (response before PGE₂ = 592±164%; during PGE₂ = 590±118%; P = NS). Infusion of sodium salicylate (SS), an inhibitor of endogenous prostaglandin synthesis, augmented acute insulin responses to glucose in normals (response before SS = 313±62%; during SS = 660±86%; P < 0.001). In adult-onset diabetes with fasting hyperglycemia, SS restored absent acute insulin responses to glucose (20 g i.v.) pulses (response before SS = 5±6%; during SS = 97±24%; P < 0.005). This was accompanied by a fourfold augmentation in second phase insulin secretion (second phase before SS = 1,696±430%; during SS = 5,176±682%; change 10-60 min insulin, μU/ml·min,% basal, P < 0.001) and by acceleration of glucose disappearance rates (K_G before SS = 0.56±0.06; during SS = 1.02±0.17%/min, P < 0.005). These findings uniquely demonstrate that (a) PGE₂ inhibits glucose-induced acute insulin responses and decreases glucose disposal in nondiabetic humans and (b) SS restores acute insulin responses, augments second phase insulin secretion, and accelerates glucose disposal in hyperglycemic, adultonset diabetics. It is hypothesized that endogenous PGE synthesis may play a role in defective insulin secretion and glucose intolerance in diabetes mellitus.

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