Studies on the effect of oral hypoglycaemic agents on hepatic glycogenolysis

Abstract

The effect of three sulphonamide derivatives, tolbutamide, acetohexamide and glycodiazine and two of the biguanide derivatives, phenformin and metformin on hepatic glycogenolysis was investigated in the rat. The in vitro studies in both normal and alloxan-diabetic rats reveal that tolbutamide, acetohexamide and glycodiazine inhibited hepatic glucose-6-phosphatase enzyme activity while phenformin and metformin produced no effect. Hepatic phosphorylase enzyme activity was inhibited by tolbutamide and glycodiazine, while acetohexamide, phenformin and metformin failed to produce any effect. The in vivo studies showed that an acute dose of any of the sulphonamide derivatives studied did not affect the two enzyme activities in both normal and alloxan-diabetic rats. However, the two biguanides, phenformin and metformin although not affecting the enzyme activities in normal animals, they produced significant decrease in glucose-6-phosphatase enzyme activity in livers of diabetic rats. The conclusion is reached that sulphonamide derivatives affect the glycogenolytic enzymes directly only in vitro , while a single, moderately big, hypoglycaemic dose produced no effect in vivo . On the other hand, the two biguanides affect glucose-6-phosphatase enzyme activity in diabetic rats by increasing glucose utilization, an effect not related to insulin.