Effect of buformin on the regulation of glycogen metabolism in the skeletal muscle of normal rats.

In view of the experience that after short- or long-term oral administration of biguanides to rats no glycogenolysis in the muscle tissue occurs or even an increase of the muscle glycogen content and a high rate of incorporation of radioglucose into the muscle glycogen, the glycogen synthetase activity of skeletal muscle in a concentrated muscle homogenate and the effect of isoproterenol on glycogenolysis were investigated in normal rats after short-term oral administration of 1-butylbiguanide (buformin). The basal synthetase activity and the ATP inhibition of the enzyme were not affected by buformin, but the cyclic AMP mediated inactivation was significantly inhibited after buformin pretreatment. This inhibition was reversed by running the assay in the presence of Mg2+. Buformin also inhibited the isoproterenol induced glycogenolysis of the skeletal muscle tissue. From our results we suppose that biguanides may influence the regulation of glycogen metabolism by inhibiting the inactivating synthetase kinase and the activating phosphorylase kinase. It is possible that divalent cations like Mg2+ as an activator of kinase reactions are concerned.