The inactivation of phosphorylase and activation of glycogen synthase in the adipose tissue.

Abstract

It has been confirmed that, upon refeeding after a prolonged fast, rats accumulate glycogen in their adipose tissue at a concentration which can reach 100-fold that of non-fasted animals. The inter-conversion of the two forms of glycogen phosphorylase and glycogen synthase has been investigated in the adipose tissue of refed animals with a methodology which makes it possible to measure phosphorylase a with little or no interference of phosphorylase b. In an extract filtered on Sephadex G-25, glycogen phosphorylase was initially predominantly in the active a form and became inactive within 20 to 60 min upon incubation of the filtrate at 25°C; this inactivation was faster in the presence of glucose, caffeine or glucose 6-phosphate and was retarded in the presence of EDTA or inorganic phosphate. In the same filtrate, glycogen synthase was initially predominantly in the inactive b form and became activated after a latency period. This latency period was shortened by all agents which favoured the inactivation of phosphorylase and was prolonged by the agents which retarded the same inactivation. The activation of glycogen synthase was also inhibited by muscle phosphorylase a. All these data are in agreement with the hypothesis that phosphorylase a is an inhibitor of synthase phosphatase in the adipose tissue. The addition of glucose or insulin to isolated fat pads caused an inactivation of phosphorylase; an activation of glycogen synthase occurred after a short latency. Mannose but not fructose had an effect similar to that of glucose. The concentration of glucose 6-phosphate in the tissue was about equally increased by incubation in the presence of glucose plus insulin or fructose plus insulin although the synthesis of glycogen and synthase activation were much greater in the first condition than in the second. The administration of glucose and insulin to anaesthetized rats caused a sequential inactivation of phosphorylase and activation of glycogen synthase in the epididymal fat in vivo.