Increase of microsomal glucose-6-phosphatase activity after chronic ethanol administration

To study the effect of chronic ethanol administration on the activity of hepatic microsomal glucose-6-phosphatase, female rats were pair-fed liquid diets with 36% of total calories either as ethanol or isocaloric carbohydrate (controls). The remainder of the diet contained 35% of total calories as fat, 18% as protein, and 11% as additional carbohydrate. Six weeks of ethanol feeding as isocaloric substitution for carbohydrate increased significantly the activity of glucose-6-phosphatase (expressed per mg microsomal protein) both in fed (38%; p < 0.001) and fasted 18%; p < 0.02) rats. When expressed per unit of body weight, the enzyme activity was increased even further both in fed (66%; p < 0.01) and fasted (43%; p < 0.01) rats. Another group of rats received diets containing 36% of calories either as ethanol or isocaloric fat. The remainder of the diet contained 11% of total calories as carbohydrate, 18% as protein, and 35% as additional fat. Six weeks of this ethanol feeding as isocaloric substitution for fat again increased glucose-6-phosphatase activity significantly. Ultracentrifugation in a Cs⁺-containing sucrose gradient to separate rough and smooth microsomes revealed that the increase in glucose-6-phosphatase activity after ethanol feeding occurred mainly in the smooth microsomal membranes.