Gluconeogenesis insulin effect

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. 

REGULATION OF GENE TRANSCRIPTION A major action of insulin is the regulation of transcription of more than 100 specific genes. InsuMn inhibits the transcription of phosphoenolpyruvate carboxykinase, contributing to insulin s inhibition of gluconeogenesis this effect of insulin may explain why the liver overproduces glucose in the insuhn-resistant state that is characteristic of type 2 DM. 

This insulin effect of growth hormone observed in vivo may also explain some of the discrepancies observed between in vivo and in vitro effects of growth hormones on glucose uptake by muscle. Whereas growth hormone inhibits glucose uptake in vitro, in vivo its inhibitory effect is compensated for by the insulin secreted as a result of liver gluconeogenesis. 

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. 

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. 

Insulin inhibits glycogenolysis and gluconeogenesis. Glucagon opposes the effects of insulin and therefore helps to maintain the blood glucose level so that it has the same end result as that of fatty acid oxidation (See Figure 12.14). 

Initially the level of insulin decreases, favouring increased rates of lipolysis, fatty acid oxidation, muscle protein degradation, glycogenolysis and gluconeogenesis. It soon increases, however, as a result of insulin resistance, when the stimulation of the above processes will depend on the cytokine levels. For details of endocrine hormone effects, see Chapter 12. For details of cytokines see Chapter 17. 

The effects of insulin on carbohydrate metabolism are discussed on p. 158. In simplified terms, they can be described as stimulation of glucose utilization and inhibition of gluconeogenesis. In addition, the transport of glucose from the blood into most tissues is also insulin-dependent (exceptions to this include the liver, CNS, and erythrocytes). 

---