Naloxone effects on post-prandial glucose, insulin and C-peptide levels in obese subjects

In order to investigate the relationships between glucose metabolism, insulin secretion and endogenous opioids in obese patients, we have studied the effects of a naloxone infusion on insulin and C-peptide release after a normal meal (800 kcal) eaten at 12.00 hr in 16 obese women, aged 20-61 yr, with a BMI ranging from 25 to 37.2 kg/m2, with normal glucose tolerance (Group 1) and with NIDDM (Group 2). Naloxone was administered in a bolus of 1.6 mg i.v., followed by a continuous infusion of 4 mg in 2 hr starting immediately after feeding. In Group 1 naloxone infusion significantly increased the glucose levels, but insulin secretion was unaffected. In Group 2, naloxone infusion failed to modify significantly the postprandial levels of glucose, insulin and C-peptide. Therefore, in our study naloxone infusion seems to have beta-endorphin-like effects in non-diabetic obese subjects by increasing their glycemic levels, with no evidence of expected insulin decrease. In diabetic obese patients we observed a trend towards decrease in glycemic values during naloxone infusion, as expected, due to insulin plasma levels increase. By these data we can hypothesise a complex regulatory role of opioids in metabolic balance in obesity. In diabetic patients, naloxone can improve the surviving insulin secretion with better glucose tolerance. In non-diabetic subjects naloxone exerts its effects, probably, on peripheral organs.