Liver Glycogen Synthesis in Intact Alloxan Diabetic Rats.

It is now clearly established that insulin controls the utilization of glucose by muscle and adipose tissue (l-4), presumably by stimulating glucose transport across an otherwise impermeable cell membrane. Although a similar role of insulin in hepatic glucose uptake seems unlikely, since the liver cell is reported to be freely permeable to both inflow and outflow of glucose (5), there is nevertheless a considerable body of evidence pointing to marked impairment of hepatic glucose utilization in diabetes (6-10). The most impressive of this evidence stems from studies with rat liver slices in vitro (ll-14), which demonstrated an almost complete suppression of the incorporation of (Y-labeled glucose into the liver glycogen of alloxan diabetic rats. These results are presumed to be due to a block in glucose phosphorylation, since comparable effects are not observed with fructose-C14. Our recent finding that hepatic glucokinase activity is low in alloxan diabetic rats (15) also argues in favor of a rate-limiting role of this enzyme in liver glycogen synthesis. However, hepatic glucokinase is also low in fasting (15), yet hepatic glycogen repletion occurs rapidly when carbohydrate is administered (16). The suggestion has also been offered recently that a block in liver glycogen synthesis in diabetes may occur at the enzyme uridine diphosphate glucose-glycogen glucosyltransferase (1720). In accord with an impairment of hepatic glycogen synthesis in diabetes, it is generally assumed that liver glycogen is low in this condition. However, a review of the available clinical and experimental data reveals that low hepatic glycogen levels in diabetes are the exception rather than the rule. Whereas liver glycogen levels may be somewhat low in the diabetic when compared with normal, fed animals, they are appreciably higher when compared in the fasted condition (21-27). These conflicting views concerning the role of insulin lack in influencing liver glycogen deposition prompted us to make a further study of glycogen synthesis in intact, alloxan diabetic rats, and the results of this investigation are reported in this communication.