Hepatic gluconeogenesis

Pilkis, S. J., El-Maghrabi, M. R., and Claus, T. H., 1988. Hormonal regulation of hepatic gluconeogenesis and glycolysis. Annual Review of Biochemistry 57 755-783. 

Central control of glucose homeostasis critically depends on the brain s ability to sense extracellular [glucose]. Within hypothalamus at least two types of neurons were identified which are presumably involved in this process. They are either glucose excited or glucose inhibited. Both types of neurons appear to be involved in the control of feeding, hepatic gluconeogenesis,... 

Pilkis SJ, Granner DK Molecular physiology of the regulation of hepatic gluconeogenesis and glycolysis. Annu Rev Physiol... 

An enhanced rate of hepatic gluconeogenesis to maintain the blood glucose level and provide the fuel for the brain and other tissues (Figure 16.9). 

Pharmacology Rosiglitazone and pioglitazone, members of the thiazolidinediones class of antidiabetic agents, improve glycemic control by improving insulin sensitivity. Studies indicate that they improve sensitivity to insulin in muscle and adipose tissue and inhibit hepatic gluconeogenesis. 

Except for one case/° recent clinically oriented MRS studies of human liver have been at 1.5T. Several studies applied in vivo MRS to diffuse liver disease. ° °" The PDE intensity was lower in cirrhosis than in controls ° and served to distinguish the alcoholic, viral, and cholestatic etiologies of diffuse liver disease. ° However, there was no difference between patients with non-alcoholic fatty liver disease (NAFLD) and controls. Sharma et al., using the relative PME intensity as a measure of altered gluconeogenesis (this peak can contain glucose-6-P and 3-phos-phoglycerate in addition to PC and PE), found that hepatic gluconeogenesis was altered in both obese and non-obese Asian Indians with NAFLD, relative to non-obese subjects without NAFLD. 

Pioglitazone hydrochloride, a thiazolidinedione, acts primarily by decreasing insulin resistance. It improves sensitivity to insulin in muscle and adipose tissue and inhibits hepatic gluconeogenesis. It also improves glycemic control while reducing circulating insulin levels. 

Individuals with chronic liver disease may have disorders of fluid and electrolyte balance, including ascites, edema, and effusions. Alterations of whole body potassium induced by vomiting and diarrhea, as well as severe secondary aldosteronism, may contribute to muscle weakness and can be worsened by diuretic therapy. The metabolic derangements caused by metabolism of large amounts of ethanol can result in hypoglycemia, as a result of impaired hepatic gluconeogenesis, and in ketosis, caused by excessive lipolytic factors, especially increased cortisol and growth hormone. 

M. Short-term leptin-dependent inhibition of hepatic gluconeogenesis is mediated by insuhn receptor substrate-2. Mol. Endocrinol., 16, 1612-1628 (2002)... 

Pllkls, S.J. Claus, T.H. (1991) Hepatic gluconeogenesis/ glycolysis regulation and structure/function relationships of substrate cycle enzymes. Annu. Rev. Nutr. 11, 465-515. 

Glucagon increases blood glucose by mobilizing liver glycogen and stimulating hepatic gluconeogenesis. 

Early studies of the stimulatory effects of glucagon on hepatic gluconeogenesis using different gluconeogenic substrates and measuring the changes in the concentrations of intermediary metabolites identified the substrate cycles between pyruvate and P-enolpyruvate and between fructose-1,6-P2 and fructose-6-P as major sites of... 

Phase 5, Prolonged Starvation In the later part of phase 4 and in phase five, plasma levels of ketone bodies increase and ketone bodies partially replace glucose as a fuel supply for the brain. This, in turn, decreases the demand for hepatic gluconeogenesis and acts to conserve muscle protein. 

Fujiwara et al. (1995) found a suppression of hepatic gluconeogenesis in long-term troglitazone treated diabetic KK and C57BL/ksJ-db/db mice. 

Bannister DW (1976a) The biochemistry of fatty liver and kidney syndrome. Biotin-mediated restoration of hepatic gluconeogenesis in vitro and its relationship to pyruvate carboxylase activity. Biochemical Journal 156, 167-73. 

Bannister DW (1976b) Hepatic gluconeogenesis in chicks effect of biotin on gluconeogenesis in biotin-deficiency and fatty liver and kidney syndrome. Comparative Biochemistry and Physiology B 53, 575-9. 

Shin DJ and McGrane MM (1997) Vitamin A regulates genes involved in hepatic gluconeogenesis in mice phosphoenolpyruvate carhoxykinase, fructose-1,6-his-phosphatase and 6-phosphofructo-2-kinase/fructose-2,6-hisphosphatase./ourna/o/ Nutrition 127,1274-8. 

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