AJP - Endocrinology and Metabolism, Vol 239, Issue 6 490-E500, Copyright © 1980 by American Physiological Society
Prostaglandin synthesis inhibitors reverse alpha-adrenergic inhibition of acute insulin response to glucose
S. A. Metz and R. P. Robertson
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.
