Prostaglandin synthesis inhibitors reverse α-adrenergic inhibition of acute insulin response to glucose

S. A. Metz, R. P. Robertson

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Prostaglandin E (PGE) has several effects on glucose homeostasis and insulin secretion. The same events can be induced by α-adrenergic stimulation, which is known to stimulate PGE synthesis. To evaluate the hypothesis that PGE may be one intracellular mediator for certain α-adrenergic events, we examined the effects of a known PG synthesis inhibitor sodium salicylate (SS) (40 mg/min iv) on the α-adrenergic effects of epinephrine (Epi) at two doses (3 and 6 μg/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, x̄ ± 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 α-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 α-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 α-adrenergic events selectively in the pancreatic islet.

Original languageEnglish (US)
Pages (from-to)E490-E500
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume2
Issue number6
StatePublished - 1980

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