Correlation between Rates and Enzyme Levels of Increased Gluconeogenesis in Rat Liver and Kidney after Partial Hepatectomy

Abstract

The metabolic rates and key enzymes of gluconeogenesis and glycolysis were determined and correlated in perfused livers, isolated hepatocyte suspensions and kidney cortex slices of rats after two-thirds hepatectomy. Fed unoperated, sham operated and fasted animals served as controls.In liver the following results were obtained. In kidney cortex the following results were obtained. Firstly, after partial hepatectomy gluconeogenesis from lactate was enhanced in tissue slices to 217 % after 24 h. Gluconeogenesis from fructose was unchanged. These rates coincided with an increase of the level of phosphoenolpyruvate carboxykinase to 193 % and of glucose-6-phosphatase to 151 %. Secondly, after a 24-h fast similar changes for the gluconeogenic rate to 200 % and of phosphoenolpyruvate carboxykinase to 240 % as well as of glucose-6-phosphatase to 136 % were observed. Thirdly, neither the rates of glycolysis nor the levels of hexokinase, phosphofructokinase and pyruvate kinase were altered after partial hepatectomy or a 24-h fast. No significant changes neither in liver nor in kidney cortex occurred after sham operation. Thus the drastic reduction of liver tissue after partial hepatectomy was compensated by an increase of gluconeogenesis in the liver remnant and in kidney cortex, both accompanied by an enhancement of the phosphoenolpyruvate carboxykinase level, in order to maintain the glucose homeostasis.

Regulation of Fructose‐Bisphosphatase Activity

“…However, a 1.5% increase in the activity of Fru-P,ase under these conditions may not necessarily be due to an increase in the net synthesis of Fru-P,ase in the kidney. The proposal of Zalitis and Pitot (1979) that Fru-P,ase may be a constitutive protein may also be supported by recent reports indicating that during the inhibition of liver gluconeogenesis by partial hepatectomy Katz, 1979) or by treatment with galactosamine , there is an increase in the rate of gluconeogenesis and an increase in the activity of phosphoenolpyruvate carboxykinase, with no change in the activity of Fru-P,ase in the kidneys of these rats. Duruibe and Tejwani (1981) observed a decrease in the activity of liver Fru-P,ase in rats starved for 48 hr.…”

Transcriptional and posttranscriptional regulation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase during liver regeneration.

“…When liver mass is reduced to -30% of its original value, an increase in gluconeogenesis and a decrease in glycolysis take place to maintain glucose homeostasis (4,5). Fru-2,6-P2, a key regulatory metabolite ofliver carbohydrate metabolism, remains low during this state (6).…”

“…In the liver that remains after partial hepatectomy there are marked changes in composition and energy metabolism even before mitotic activity increases. Hepatic metabolism is shifted from utilization of carbohydrates to increased utilization of lipids (3), and gluconeogenesis increases while glycolysis decreases to maintain glucose homeostasis (4,5). During this process, fructose 2,6-bisphosphate (Fru-2,6-P2), the most potent allosteric activator of 6-phosphofructo-1-kinase (PFK-1, EC 2.7.1.11) and inhibitor of fructose-1,6-bisphosphatase (FBPase-1, EC 3.1.3.11), is markedly decreased, resulting in an inhibition of PFK-1 and activation of FBPase-1 (6).…”

Role of Metabolic Overload in the Initiation of DNA Synthesis following Partial Hepatectomy in the Rat

“…Why Junge and C'reutzfeldt [16] did not record at 24 h any regeneration im pairment after hypertonic glucose infusion and this with or without increasing doses of insulin or glucagon is more puzzling and could possibly be due to the lower amount of glucose infused (one-third of the present dose) or to more subtle technical differences related to operative stress. It can be specu lated that glucose infusion suppresses the re quirement for the remaining liver to produce more glucose [18] allowing the maintenance of hepatic ATP, glucogcn and fatty acids. The suppression of posthepatcctomy hypoglyce mia can also be expected to modify the hor monal response to PH, namely the secretion of insulin and glucagon.…”