The Effects of Glucose and Fructose on Glycogen Metabolism in the Isolated Perfused Rat Liver

Glycogen metabolism is considered to be regulated by the activities of the a forms of glycogen synthase and phosphorylase. Among other factors, the concentration of circulating blood glucose controls the activities of these two enzymes. It has been shown in experiments in oivo (De Wulf & Hers, 1967; Stalmans et al., 1974), isolated perfused liver (Buschiazzo et al., 1970; Glinsmann et al., 1970) and isolated hepatocytes (Walli et al., 19746) that high glucose concentrations increase the activity of glycogen synthase a and lower the activity of phosphorylase a. Since these glucose concentrations greatly exceed that of the circulating glucose, we investigated whether these same effects could be elicited by near-physiological concentrations. All experiments were performed on fed rats. The perfusion technique and the methods for the assay of enzyme activities, glycogen content and metabolites have been described previously (Schimassek, 1963; Walli et a/., 1974~). Livers from fed rats were perfused with medium containing a n initial glucose concentration of 2-3 mM. After an equilibration period of 60min, the glucose concentration in the medium was between 7 and 9 m ~ . Additional glucose (5 -8m~) was then added to the medium. Samples of liver were then taken at various time-intervals for the measurement of enzyme activities and liver glycogen. At 5 min after addition of glucose, the activity of liver phosphorylase a was lowered by about 58 % and that of glycogen synthase a increased (Table 1). After lOmin the lowest activity of phosphorylase a was observed, whereas that of glycogen synthase a had increased nearly twofold. However, after 60min the enzyme activities had returned to their normal values. The glucose concentration at 10 and 60min after the addition of glucose did not change significantly; also no appreciable changes in the glycogen content in the liver were noted. Thus even though glucose significantly alters the activities of phosphorylase a and glycogen synthase a, it does not bring about net glycogen synthesis. We have previouslysuggested (Walli etal., 1974a) that theactual content and the molecular configuration of the glycogen in the liver may play an important role in glycogen synthesis. If livers have a low initial glycogen content or if they are first subjected to glycogenolysis by mild hypoxia, glucagon or adrenaline treatment to lower the glycogen content, and then perfused with fructose or sorbitol (500,~mo1/60min infused in