Effect of Ethanol on Stimulus-induced Insulin Secretion and Glucose Tolerance: A Study of Mechanisms

Abstract

The effect of ethanol on stimulus-induced insulin secretion was studied, and possible mechanisms were examined in fasting unanes-thetized and unrestrained rats with indwelling jugular and aortic catheters. Glucose (150 mg.) or tolbutamide (10 mg.) was given rapidly, i.v., one hour after a gavage of ethanol or saline (control). Acutely, ethanol treatment caused marked inhibition of glucose-induced insulin secretion and impaired glucose disappearance rate. Tolbutamide-induced insulin secretion was also significantly inhibited, and decline in glucose was significantly less in ethanol-treated rats. In response to ethanol, serum calcium concentration significantly declined for two hours. In another study, an ethanol metabolite, acetate (0.4 μmole/min.) or vehicle (control) was infused for 60 minutes prior to 150 mg. glucose pulse. Acetate priming significantly potentiated glucose-induced insulin secretion and also improved glucose tolerance. It is proposed that (1) ethanol in vivo acutely induces hypocalcamie, which inhibits glucose- and tolbutamide-induced insulin secretion—which, in turn, causes glucose intolerance and prevents tolbutamide-induced hypoglycamie. (2) Acetate might be the actual potentiating influence on glucose-induced insulin secretion observed several hours after ethanol treatment.