Beta-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 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.
Giugliano
D
D
First Faculty of Medicine, University of Naples, Italy.
Cozzolino
D
D
Ceriello
A
A
Salvatore
T
T
Paolisso
G
G
Torella
R
R
D000328:Adult; D000700:Analgesics / Q000494:pharmacology; D001241:Aspirin / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000097:blood / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology; D005260:Female; D005934:Glucagon / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008239:Lysine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D011453:Prostaglandins / Q000378:metabolism; D013806:Theophylline / Q000494:pharmacology; D001615:beta-Endorphin / Q000494:pharmacology / Q000502:physiology*
D000700:Analgesics; D007328:Insulin; D011453:Prostaglandins; D001615:beta-Endorphin; D005934:Glucagon; D013806:Theophylline; D000242:Cyclic AMP; D005947:Glucose; D008239:Lysine; D001241:Aspirin; D002118:Calcium; C010395:acetylsalicylic acid lysinate