Gluconeogenesis control

See also Action of Insulin (from Chapter 23), Gluconeogenesis, Control of Fatty Acid Synthesis, Hormonal Regulation of Fuel Metabolism, Figure 5.21, Table 23.2... 

Gluconeogenesis Is Regulated by Allosteric and Substrate-Level Control Mechanisms... 

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,... 

GLYCOLYSIS (solid lines) and GLUCONEOGENESIS (dotted lines) share some common enzymes, but they diverge around the control steps. Major control enzymes are boxed. Signals that turn glycolysis on turn gluconeogenesis off, and vice versa. 

Pittner, R.A., Fears, R. and Brindley, D.N. (1985). Effects of glucocorticoids and insulin on activities of phosphatidate phosphohydrolase, tyrosine aminotransferase and glycerol kinase in isolated rat hepatocytes in relation to the control of triacyglycerol synthesis and gluconeogenesis. Biochem. J. 225 455—462. 

The interconversion of fructose-6-phosphate and fructose-1,6 bis phosphate is a control point in glycolysis and gluconeogenesis. Gluconeogenesis is a pathway which allows carbon atoms from substrates such as lactate, glycerol and some amino acids to be used for the synthesis of glucose, so it is in effect physiologically the opposite of... 

Having now considered the principles of metabolic regulation, we can turn our attention to some real pathways and study how the theory is put into practice. Further details of the control reactions of glycolysis and gluconeogenesis are given in Section 6.4.2. 

Pyruvate dehydrogenase is inhibited by its product acetyl CoA. This control is important in several contexts and shoidd be considered along with pyruvate carboxylase, the other mitochondrial enzyme that uses pyruvate (introduced in gluconeogenesis, Chapter 14, Figure 1-14-5). 

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. 

R. Iyengar (1986). Structural characterization of the glucagon receptor. In N. Kraus-Friedman (Ed.). Hormonal Control of Gluconeogenesis, vol. 2. Boca Raton CRC Press, pp. 21-34. 

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. 

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