β-Endorphin and islet hormone release in humans: Evidence for interference with cAMP

The present studies were undertaken to characterize further the influence of synthetic human β-endorphin (0.5 mg/h) on insulin and gluccagon responses to intravenous glucose in humans. Infusion of β-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 <0.01) vs. saline 1.82 ± 0.15%/min]. Glucose-induced glucagon suppression was significantly lower during β-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 β-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 β-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 β-endorphin on insulin secretion. These data confirm that β-endorphin stimulates glucagon and inhibits basal and glucose-stimulated insulin secretion and suggest that the opioid influences the intraislet adenylate cyclase activity.