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

Glucose synthesis and enzymatic activities of various CO₂-fixing enzymes have been studied in normal and diabetic liver preparations. A three-fold increase in pyruvate carboxylase and α-ketoglutarate carboxylase has been observed in alloxan-diabetic, anti-insulin serum and cortisol treated liver preparations as compared to normal. The increased glutarate carboxylase activity was found to be localized in the mitochondrial fraction. In addition a sixfold 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, oxaloacetate utilization was found to be increased in diabetic and cortisol treated rat livers. Based on these results a pathway for gluconeogenesis has been 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.