Studies on Mechanism of Glucose Synthesis in Diabetic and Normal Rat Liver

Abstract

Glucose synthesis and enzymatic activities of various CO2-fixing enzymes were studied in normal and diabetic liver preparations. A 3-fold increase inpyruvate carboxylase and a-ketoglutarate carboxylase was observed in alloxan-diabetic, anti-insulin serum and cortisol treated liver preparations as compared to normal. The increased glutarate carboxylase activity was localized in the mitochondrial fraction. In addition a 6-fold increase in phosphoenolpyruvate carboxykinase was observed. Studies on net glucose synthesis show that combination of pyruvate and glutamate are far more effective than any single substrate. Furthermore, oxalo-acetate utilization was increased in diabetic and cortisol treated rat livers. Based on these results a pathway for gluconeogenesis was formulated. It is suggested that increased gluconeogenesis observed in diabetic animals involves CO2 fixation with pyruvate and glutamate giving rise to increased formation and utilization of oxaloacetate.