Hyperglycemia and obesity as determinants of glucose, insulin, and glucagon responses to β-endorphin in human diabetes mellitus

The effect of human β-endorphin on plasma glucose, insulin, and glucagon concentrations was studied in patients with noninsulin-dependent diabetes mellitus and in normal subjects. The subjects were divided according to their body weight into lean (body mass index, <25) and obese (body mass index, > 29.5) groups. In lean subjects, infusion of 0.5 mg/h β-endorphin caused significant increases in peripheral plasma glucose and glucagon levels, but no change in plasma insulin. In obese subjects, there was an immediate marked increase in both plasma insulin and glucagon concentrations during the β-endorphin infusion, but the plasma glucose response was lower than that of lean subjects. In lean diabetic patients, β-endorphin produced significant simultaneous increments in both insulin and glucagon concentrations and significantly decreased plasma glucose levels. These hormonal responses to β-endorphin were amplified in the obese diabetic patients. There was a significant correlation (r = 0.61; P <0.01) between fasting plasma glucose levels and the integrated insulin area in response to β-endorphin. The infusion of a lower dose of β-endorphin (0.05 mg/h) in diabetic patients produced similar increments in both insulin and glucagon levels and also decreased plasma glucose concentrations. These results indicate that β-endorphin may have important glucoregulatory effects in man depending on the dose administered, the presence of obesity, and the prevailing plasma glucose concentration.