The regulation of insulin and glucagon secretion by opiates: a study with naloxone in healthy humans.

The presence of beta-endorphin and enkephalin in pancreatic islets suggests that opioid peptides may play a role in the regulation of pancreatic endocrine function. Since data in the literature are rather controversial, we examined the effects of different doses of naloxone on insulin and glucagon secretion in 21 healthy nonobese volunteers (6 women and 15 men) by measuring the variations of insulin and glucagon plasma levels following a 5-g i.v. glucose load before and during a 30-min naloxone infusion. Total amounts of 0.4 and 0.8 mg of naloxone failed to modify serum insulin and plasma glucose responses to glucose challenge. On the contrary, 0.2 mg/kg (i.e. 12-14 mg per subject as total amount) given to 3 women and 6 men led to a glucose-induced insulin release significantly lower than that recorded in basal conditions, with corresponding greater plasma glucose elevation. The suppressive effect of glucose on glucagon concentration was less pronounced during naloxone. Data reported here suggests that inhibition of opiate receptors in human pancreas occurs only with large amounts of naloxone. Moreover, they may indirectly support the stimulatory role of opioid peptides on insulin secretion in man, according to some experimental in vitro and in vivo studies. In addition, naloxone seems to reduce pancreatic A-cell sensitivity to hyperglycemia.