Translocation and aggregation of hepatic glycogen synthase during the fasted-to-refed transition in rats.

Changes in the activation state and intracellular distribution of liver glycogen synthase have been studied during the fasted-to-refed transition in rats. Glycogen synthase activity and activation state were measured in supernatants and pellets obtained after centrifugation of liver homogenates at 9200 g. Upon refeeding, the glycogen synthase activity ratio increased, in a time-dependent manner, in both fractions. The total activity of the enzyme decreased in supernatants and was quantitatively recovered in the pellets. Therefore, refeeding induced both the activation of glycogen synthase and its translocation from the soluble to the pelletable fraction. Immunocytochemical evidence indicates that refeeding induced the formation of clusters of glycogen synthase, which were recovered in the 9200 g sediments. However, the enzyme clusters did not locate with the glycogen particles in the pelletable fraction. The glycogen synthase activation state responded almost as an of-off switch to changes in the intracellular glucose 6-phosphate concentration in the range 0.2-0.3 mM. The amount of enzyme present in the pellets correlated linearly with the intracellular glucose 6-phosphate levels. These results indicate that glucose 6-phosphate is the key signal for both the activation and changes in intracellular localization of hepatic glycogen synthase in vivo.