Gluconeogenesis inhibition

Fructose 1,6-biphosphatase Involved in gluconeogenesis inhibition by lithium of unknown relevance... 

Glucocorticoids have an anti-insulin effect and aggravate the pathologic consequences of diabetes mellitus. They increase gluconeogenesis, inhibit the peripheral utilization of glucose, and cause hyperglycemia and glucosuria. Cortisol s effect, for example, is opposite to that of insulin s. 

Acetyl-CoA is a potent allosteric effector of glycolysis and gluconeogenesis. It allosterically inhibits pyruvate kinase (as noted in Chapter 19) and activates pyruvate carboxylase. Because it also allosterically inhibits pyruvate dehydrogenase (the enzymatic link between glycolysis and the TCA cycle), the cellular fate of pyruvate is strongly dependent on acetyl-CoA levels. A rise in... 

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,... 

Under certain circumstances, and very rarely, the inhibition of gluconeogenesis by metformin may suppress lactic acid metabolism and precipitate a potentially fatal lactic acidosis. Impairment of renal function, liver disease, alcoholism, conditions that give rise to increased lactate production (e.g. congestive heart failure, infections) are therefore contraindications for the application of metformin. 

Sherratt, H.S.A. (1981). Inhibition of gluconeogenesis by non-honnonal hypoglycaemic compounds. In Shott-Tenn Regulation of Liver Metabolism (Hue. L. Van de Werve, G.. eds.), pp. 119-227, Elsevier/North Holland Biochemical Press, Amsterdam. 

Increased fatty acid oxidation is a characteristic of starvation and of diabetes meUims, leading to ketone body production by the Ever (ketosis). Ketone bodies are acidic and when produced in excess over long periods, as in diabetes, cause ketoacidosis, which is ultimately fatal. Because gluconeogenesis is dependent upon fatty acid oxidation, any impairment in fatty acid oxidation leads to hypoglycemia. This occurs in various states of carnitine deficiency or deficiency of essential enzymes in fatty acid oxidation, eg, carnitine palmitoyltransferase, or inhibition of fatty acid oxidation by poisons, eg, hypoglycin. 

In adipose tissue, the effect of the decrease in insulin and increase in glucagon results in inhibition of lipo-genesis, inactivation of lipoprotein lipase, and activation of hormone-sensitive lipase (Chapter 25). This leads to release of increased amounts of glycerol (a substrate for gluconeogenesis in the liver) and free fatty acids, which are used by skeletal muscle and liver as their preferred metabolic fuels, so sparing glucose. 

Goldstein, R.S., Contardi, L.R., Pasino, D.A. and Hook, J.B. (1987). Mechanisms mediating cephaloridine inhibition of renal gluconeogenesis. Toxicol. Appl. Pharmacol. 87(2) 297-305. 

Nutrient homeostasis cell uptake of glucose (especially important in adipose and muscle), amino acids (all cells) and fatty acids stimulation of glycolysis but inhibition of gluconeogenesis (liver), synthesis of glycogen (liver and muscle), triglyceride (liver and adipose) and protein (all cells) ... 

Answer C. Insulin increases glucose transport in only two tissues, adipose and muscle. The major site of glucose uptake is muscle, which decreases hyperglycemia. Glucose and ketone transport and metabolism are insulin independent in the brain (choice D). Insulin would slow gluconeogenesis (choice A) and fatty acid release from adipose (choice B). Insulin would inhibit glycogenolysis in the liver (choice E). 

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). 

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