β-Endorphin and islet hormone release in type-2 diabetes mellitus. The effects of normoglycemia, enkephalin, naloxone and somatostatin

The present study was aimed at characterizing the effects of beta-endorphin on plasma glucose, insulin and glucagon plasma levels in subjects with type-2 diabetes mellitus. Infusion of 0.5 mg/h human beta-endorphin produced significant and simultaneous increments in both insulin and glucagon concentrations and decreased plasma glucose levels (- 18 ± 4 mg/dl, 60 min level, p <0.01). When the same diabetics were rendered euglycemic by an insulin infusion (1 mU/kg/min), beta-endorphin did not produce the expected decrease in plasma glucose concentrations nor raise plasma insulin levels; only the response of glucagon was preserved. Normal subjects were rendered hyperglycemic by an intravenous glucose infusion to match the plasma glucose levels of diabetic subjects. In this condition, beta-endorphin produced a significant increase of insulin concentrations, whereas glucagon remained suppressed. The intravenous administration of the long-acting met-enkephalin analogue DAMME (0.25 mg) blunted the hormonal responses to the subsequent beta-endorphin infusion in diabetic patients, although the inhibition was short-lived (30-40 min). Naloxone (5 mg), an opiate antagonist, did not produce any significant change in the insulin and glucagon responses to beta-endorphin, while somatostatin (0.25 mg/h) completely abolished the hormonal responses to the opioid. These results indicate that 1) beta-endorphin increases insulin and glucagon concentrations and lower plasma glucose in type-2 diabetic subjects; 2) The insulin-releasing effect of beta-endorphin is dependent on the prevailing plasma glucose levels, since it is inhibited during normoglycemia in diabetics and appears in normal subjects rendered hyperglycemic by a glucose infusion; 3) enkephalin, another endogenous, pancreatically-produced opioid peptide, counteracts the effects of beta-endorphin on islet hormone release; and 4) naloxone, an opiate antagonist, has no influence upon the metabolic and hormonal responses to beta-endorphin. Opioid peptides influence the secretion of insulin and glucagon in human diabetes mellitus.