Effect of Hormones on Hepatocyte Gluconeogenesis in Different Models of Acute Uraemia

Abstract

Hepatocytes isolated from the livers of starved, sham-operated, bilaterally nephrectomised and ureter-ligated rats as well as rats with ischaemic acute renal failure were used for a comparative study of the effects of different hormones on gluconeogenesis. In all tested groups dibutyryl-3′: 5′-adenosine monophosphate inhibits glucose synthesis from pyruvate whereas this process is not affected by glucagon and only slightly activated by adrenalin. In contrast, gluconeogenesis from dihydroxyacetone was stimulated by all three hormones at the expense of the conversion of dihydroxyacetone to lactate. In the presence of I-serine adrenalin, glucagon and dibutyryl cAMP also stimulate glucose synthesis, which is more marked in bilaterally nephrectomised and ureter-ligated animals. In half of the experiments with bilaterally nephrectomised rats (group BN 2), lack of sensitivity of hepatocytes to all tested hormones on gluconeogenesis from serine or dihydroxyacetone was observed. The beta-adrenergic antagonist propranolol reduced the stimulatory effect of adrenalin on glucose synthesis from serine and abolished the influence of catecholamines in the presence of dihydroxyacetone and pyruvate. This suggests that both alpha- and beta-receptors are involved in the activation of hepatic gluconeogenesis. Insulin and parathyroid hormone did not change the rate of glucose synthesis in any of the experimental groups.

Role of Energy Charge and Redox State for Hepatocyte Gluconeogenesis of Acutely Uremic Rats

“…In contrast, glucose synthesis from pyru vate was inhibited in the presence of dibutvryl cAMP. whereas this process was not affected by glucagon [3,4j. Insulin and parathyroid hormone did not change the rate of glucose synthesis [3].…”

“…Glucagon-stimulated gluconeogenesis, however, was enhanced in isolated hepatocytcs of rats with various models of acute uremia using serine or dihydroxyacetonc as substrates [3]. In contrast, glucose synthesis from pyru vate was inhibited in the presence of dibutvryl cAMP.…”

Release of Granulocyte Proteinases during Hemodialysis

“…On the other hand, hepatic gluconeogenesis is enhanced during renal insufficiency [3][4][5], Two possible causes of the reported increase in intradialytic protein catabolism [6] would be gluconeogenesis to replace glucose loss (during glucosefree dialysis) and protein breakdown to replace amino acid loss [7]. Glucose was found to be ineffective in reducing dialysis-induced catabolism.…”