The Sequential Inactivation of Glycogen Phosphorylase and Activation of Glycogen Synthetase in Liver after the Administration of Glucose to Mice and Rats

The use of anesthetized animals and of quick‐freezing techniques has allowed to obtain a reliable estimation of the level of phosphorylase a in the liver. A striking inverse relationship was observed between the levels of phosphorylase a and of synthetase a in the liver of fed mice; this observation is in agreement with the hypothesis that the inactivation of phosphorylase is a prerequisite to the activation of glycogen synthetase. Accordingly, the administration of glucose to fed rats caused an extensive inactivation of liver phosphorylase which was usually terminated within two minutes; glycogen synthetase became activated only when and if the level of phosphorylase a had been taken down below a threshold value equal to approximately 10% of the total phosphorylase. This threshold is of the same magnitude in mice. Glucose also caused a slight decrease in the activity of liver phosphorylase when the animals had been previously treated with glucagon. These observations are adequately explained by the previously described stimulation of the phosphorylase phosphatase reaction by glucose and inhibition of synthetase phosphatase by phosphorylase a . In some experiments, insulin caused a partial inactivation of phosphorylase in the liver of rats but more often was without effect, whereas a subsequent load of glucose caused the usual precipitous response, demonstrating that this effect of glucose was not mediated by insulin.