Role of Glucose-6-phosphatase in Hepatic and Renal Gluconeogenesis

Comparison of the effects of a high fat and high protein diet on the capacity for glucose formation from pyruvate and glycerol was investigated in vivo and in vitro. Ratios of radioactivity incorporated from either pyruvate-3-¹⁴C or glycerol-l-¹⁴C into blood glucose to those into expired CO₂ were higher in both groups fed the high fat and the high protein diet than those in a group fed a high carbohydrate diet. Gluconeogenesis from pyruvate and glycerol by liver slices were both increased significantly in rats fed the high fat diet, while feeding the high protein diet caused increase of renal gluconeogenesis from pyruvate and glycerol. The activities of hepatic and renal glucose-6-phosphatase(s) were changed in a similar fashion to changes in hepatic and renal gluconeogenesis, respectively.

In addition, the response of the activity of hepatic glucose-6-phosphatase with high dietary fat was more rapid than that of the activity of renal glucose-6-phosphatase with high dietary protein. Furthermore, the intraperitoneal injection of actinomycin-D to rats resulted in decrease of the activities of renal glucose-6-phosphatase of both groups fed the high fat and the high protein diet, but no significant change of the activity of hepatic glucose-6-phosphatase was observed among dietary groups.

These findings suggested that the increases in the overall flow of metabolites towards glucose formation by feeding the high fat and the high protein diet might be based on the action of different mechanisms which regulate the activities of glucose-6-phosphatase(s) of the liver and kidney.