alexa A role for prostaglandin E in defective insulin secretion and carbohydrate intolerance in diabetes mellitus.
Diabetes & Endocrinology

Diabetes & Endocrinology

Journal of Diabetes & Metabolism

Author(s): Robertson RP, Chen M

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Abstract Prostaglandin E(2) (PGE(2)) infusion in normal humans inhibited acute insulin responses to a glucose (5 g i.v.) pulse (response before PGE(2) = 593 +/- 104\%; during PGE(2) = 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 PGE(2) = 0.73+/-0.07; during PGE(2) = 0.49+/-0.06\%/min, P < 0.025). Acute insulin responses to arginine (2 g i.v.) were not affected by PGE(2) (response before PGE(2) = 592+/-164\%; during PGE(2) = 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, muU/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) PGE(2) 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.
This article was published in J Clin Invest and referenced in Journal of Diabetes & Metabolism

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