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.

Effects of buformin on the metabolsim of the isolated haemoglobin-free perfused hindlimb of normal rats.

Using the isolated, haemoglobin-free, perfused resting hindlimb of normal rats buformin neither had a direct insulin-like effect on glucose uptake by muscle tissue nor potentiated the effect of insulin on glucose uptake after oral pretreatment for one or several days with low and high doses (30 mg-350 mg/kg). Effects on glycogenolysis could not be detected. Glycerol release was inhibited after several days of pretreatment with low and high doses of buformin. The utilization of added oleate was also partly inhibited. The level of energy rich phosphates in the muscle tissue and oxygen consumption were not affected under any of the conditions used in these experiments.