Prostaglandin synthesis inhibitors reverse alpha-adrenergic inhibition of acute insulin response to glucose.
Prostaglandin E (PGE) has several effects on glucose homoeostasis and insulin secretion. The same events can be induced by alpha-adrenergic stimulation, which is known to stimulate PGE synthesis. To evaluate the hypothesis that PGE may be one intracellular mediator for certain alpha-adrenergic events, we examined the effects of a known PG synthesis inhibitor Sodium salicylate (SS) (40 mg/min iv) on the alpha-adrenergic effects of epinephrine (Epi) at two doses (3 and 6 micrograms/min) in normal male subjects. The lower dose of epinephrine diminished the acute insulin response (AIR) after a 20-g intravenous glucose pulse (control, 463 +/- 149; epinephrine, 97 +/- 38% of basal insulin, mean +/- SE, n = 6, P < 0.02); SS markedly augmented the AIR during epinephrine towards control values (339 +/- 137%; P < 0.02). In 12 subjects, the higher dose of Epi abolished the AIR. When similar studies were performed during a SS infusion, the AIR was partially restored (96 /+- 27% of basal insulin, n = 12, P < 0.01). Similarly, partial reversal of this alpha-adrenergic effect of Epi was observed with indomethacin, another inhibitor of PG synthesis. At both doses of Epi, SS augmented the glucose disappearance rate (KG) after the glucose pulse (P < 0.001). Sodium salicylate also increased basal glucagon levels (P < 0.05). In contrast, SS did not affect the glycemic response, the suppression of basal insulin levels, or the hemodynamic responses induced by adrenergic stimulation. We conclude that two prostaglandin synthesis inhibitors partially reverse the alpha-adrenergic inhibition of the AIR to glucose caused by Epi, without affecting other adrenergic events. The data are compatible with a role for prostaglandins in alpha-adrenergic events selectively in the pancreatic islet.
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007328:Insulin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011458:Prostaglandins E / Q000502:physiology*; D011941:Receptors, Adrenergic / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D012980:Sodium Salicylate / Q000494:pharmacology
D001786:Blood Glucose; D007328:Insulin; D011458:Prostaglandins E; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D003000:Clonidine; D012980:Sodium Salicylate; D007213:Indomethacin; D004837:Epinephrine