AJP - Endocrinology and Metabolism, Vol 257, Issue 3 E361-E366, Copyright © 1989 by American Physiological Society
Beta-endorphin and islet hormone release in humans: evidence for interference with cAMP
D. Giugliano, D. Cozzolino, A. Ceriello, T. Salvatore, G. Paolisso and R. Torella
First Faculty of Medicine, University of Naples, Italy.
The present studies were undertaken to characterize further the influence
of synthetic human beta-endorphin (0.5 mg/h) on insulin and glucagon
responses to intravenous glucose in humans. Infusion of beta-endorphin in
10 normal volunteers caused a clear-cut inhibition of the overall insulin
responses to a glucose pulse (0.33 g/kg iv) with values of glucose
disappearance rates in the diabetic range [0.89 +/- 0.09 (P less than 0.01)
vs. saline 1.82 +/- 0.15%/min]. Glucose-induced glucagon suppression was
significantly lower during beta-endorphin, a fact that could have
contributed to the reduced glucose utilization rates. The infusion of
theophylline (150 mg + 350 mg/h) to increase the intracellular cAMP
activity by inhibiting phosphodiesterase completely reversed the inhibitory
effect of beta-endorphin on glucose-induced insulin secretion. As a
consequence, glucose disappearance rates rose to 1.77 +/- 0.18%/min.
Theophylline did not influence significantly the glucagon-releasing effect
of beta-endorphin as well as the reduced glucagon suppression. An infusion
of exogenous calcium (100 mg as iv bolus + 5 mg/min) to raise serum calcium
in the hypercalcemic range (15 mg/dl) and lysine acetylsalicylate (72
mg/min) to block the synthesis of endogenous prostaglandin E did not
interfere with the inhibiting effect of beta-endorphin on insulin
secretion. These data confirm that beta-endorphin stimulates glucagon and
inhibits basal and glucose-stimulated insulin secretion and suggest that
the opioid influences the intraislet adenylate cyclase activity.
