Endogenous Opiates Modulate Insulin Secretion in Flushing Noninsulin-Dependent Diabetics*

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Abstract
The effects of endogenous opiates on hormonal responses to oral glucose challenge were determined in noninsulin- dependent diabetics (NIDD). In one group of subjects, facial flushing occurred in response to the administration of alcohol and chlorpropamide. The facial flushing response can be produced by an opioid peptide analog and can be blocked by naloxone. Such chlorpropamide alcohol flushing (CPAF)-positive patients are thought to represent a significant subset (>one third) of all NIDD patients who may have different severity and incidence of diabetic complications than patients who do not flush (CPAF negative). Nine NIDD patients who had never been treated with insulin and were not massively obese (2, 40% carbohydrate diet, all patients underwent two standard 100-g oral glucose tolerance tests (OGTT), one of which was accompanied by a 3-h continuous iv infusion of naloxone at 0.1 mg/min after an 0.8-mg iv loading dose of naloxone. The five CPAF-positive patients demonstrated a 50% decrease in integrated insulin secretion during the infusion of naloxone, with significant differences (P < 0.01) in insulin levels at 1,2, and 3 h of the OGTT. There were no differences in mean basal insulin or mean basal or stimulated plasma glucose levels in these patients. The four CPAF-negative patients demonstrated significantly less insulin secretion at 1, 2, and 3 h of the OGTT than the CPAF-positive group did without naloxone treatment. There were no significant effects of naloxone on insulin secretion in the CPAF-negative group. These data suggest that endogenous opiates stimulate insulin secretion in CPAF-positive noninsulin-dependent diabetics at either a central or a pancreatic level. Decreased stimulation by endogenous opiates or resistance to the effects of endogenous opiates may be a factor in the disease progression of noninsulin-dependent diabetes mellitus. {J Clin Endocrinol Metab54: 693,1982)