Chronic Ethanol Consumption and Liver Glycogen Synthesis

Chronic ethanol consumption results in a dramatic decrease in liver glycogen concentrations, which could be related to either a depressed rate of synthesis or an increased rate of breakdown. Earlier studies suggested that there is not an increase in the rate of glycogenolysis as glycogen phosphorylase activities are not elevated. In the present study it was observed that the incorporation of radiolabeled glucose into glycogen was significantly depressed in hepatocytes from ethanol-fed rats under both anaerobic and aerobic conditions. Chronic ethanol consumption decreased the total glycogen synthase (a + b) activity, which correlated closely with a loss in glycogen synthase protein. However, glycogen synthase messenger RNA levels were not depressed, which indicated posttranscriptional modifications affecting both activity and protein levels. The concentration of glucose transporter 1 was also decreased due to ethanol consumption, but glucose transporter 2 levels were not altered. This latter result suggests that glucose transport in the perivenous region of the liver lobule may be decreased in chronic ethanol consumers. The alterations in glucose transport protein and glycogen synthesis observed in this study may contribute to lowered glycogen synthesis, but do not appear to account for the magnitude of the decreases in glycogen levels and rate of synthesis. Indeed, ethanol effects on glycogen metabolism are likely to be exerted at several levels, including posttranslational modulation of enzyme activities.