1-Deoxynojirimycin and related compounds inhibit glycogenolysis in the liver without affecting the concentration of phosphorylase a.

Administration in vivo of the alpha-glucosidase inhibitors 1-deoxynojirimycin and its derivatives BAY m 1099 (miglitol) and BAY o 1248 resulted in a dose- and time-dependent decrease in the rate of hepatic glycogenolysis induced by glucagon. This represents a direct effect on the liver, since it could be reproduced on isolated hepatocytes. The amount of glucose produced by hepatocytes over a period of 10-20 min after addition of glucagon was decreased by about 70, 60 and 45% in the presence of maximally effective concentrations of BAY o 1248, deoxynojirimycin, and BAY m 1099, respectively. Half-maximal effects were observed at inhibitor concentrations between 20 and 100 microM. The concentrations of phosphorylase a and glycogen synthase a were not affected by inclusion of the alpha-glucosidase inhibitors in the hepatocyte suspensions. Thus, the antiglycogenolytic action of these compounds is not mediated by an altered activation state of the rate-limiting enzymes of glycogenolysis and of glycogen synthesis.