Opiate receptors and the metabolic response to intravenous glucose.

The role of opiate receptors in the metabolic response to an intravenous glucose load was determined in eight non-diabetic subjects (four of whom showed a positive chlorpropamide alcohol flush response and four who did not). Subjects were studied in a double blind randomised fashion receiving either a saline control or the specific opiate receptor antagonist, naloxone (0.4 mg/min), as an infusion for 5 minutes before and 20 minutes after an intravenous bolus of glucose (0.5 g/kg body weight). Naloxone decreased the early plasma glucose peak in all subjects by increasing the distribution volume but did not alter the fractional glucose clearance. Insulin and glucagon responses to glucose were not altered by naloxone. Naloxone delayed the normal post-glucose rise in the levels of the gluconeogenic precursors alanine, lactate, pyruvate and glycerol suggesting a delay in the usual inhibition in gluconeogenesis following a glucose load. There was no difference in the metabolic response between those subjects who were liable to chlorpropamide alcohol flushing and those who were not either with or without naloxone. We conclude that opiate receptors may influence distribution volume and gluconeogenesis but do not play a major role in either insulin or glucagon secretion or in glucose disposal following an intravenous glucose load.