Glycogen Synthesis from Glucose, Glucose-6-phosphate, and Uridine Diphospha Te Gl

The function of insulin as a regulator of permeability of cell membranes is, at present, in the foreground of attention. Nevertheless, experiments such as those reported in the lucid paper by Kipnis and Corin on the change of the temperature coefficient for pentose transfer into diaphragm with insulin addition indicate a possible shift from diffusion to a chemical and therefore probably enzymatic reaction. Such observations suggest that the search for a possible primary metabolic effect of insulin should not yet be fully abandoned. These considerations led us to investigate pigeon breast muscle, where Krebs had found effects of insulin on respiration maintenance' which had been confirmed.3 The fact that such an effect appeared to be unique with pigeon muscle seemed, essentially, not to argue against its possibly reflecting an aspect of insulin activity. Although with the pigeon breast muscle system no insulin effect could be obtained when measuring glycogen synthesis, we continued because we became aware, during these studies, of some seemingly unresolved problems in the field of glycogen synthesis proper. Certain problematic aspects of the relation of phosphorylase to glycogen synthesis had been brought out already through work on the epinephrine effect on phosphorylase activity. This work, done mainly by Sutherland and his co-workers4-6 and by Cori,7 showed clearly that phosphorylase activation invariably led to glycogen breakdown and never to glycogen synthesis. Since our experiments with breast muscle homogenates gave strong support to the proposition that phosphorylase was not involved in glycogen synthesis, we considered the possibility that the synthesis might go by way of LUDPG. The demonstration by Leloir8 that liver contains an enzyme which will form glycogen from UDPG, made it seem likely that the problem of muscle glycogen synthesis could be explained in te'rms of a UDPG pathway. In the experiments reported below, results with the pigeon breast muscle homogenate are described, and preliminary data are given on the rabbit and rat skeletal muscle system which synthesizes glycogen from UDPG.