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 unanesthetized and unrestrained rats with indwelling jugular and aortic catheters. Glucose (150 mg.) or tolbutamide (10 mg.) was given rapidly, i.v., one hour after agavage 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 micronmole/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 hypocalcemia, which inhibits glucose- and tolbutamide-induced insulin secretion--which, in turn, causes glucose intolerance and prevents tolbutamide-induced hypoglycemia. (2)Acetate might be the actual petentiating influence on glucose-induced insulin secretion observed several hours after ethanol treatment.