Glucose transport insulin, effect

The insulin receptor is a transmembrane receptor tyrosine kinase located in the plasma membrane of insulin-sensitive cells (e.g., adipocytes, myocytes, hepatocytes). It mediates the effect of insulin on specific cellular responses (e.g., glucose transport, glycogen synthesis, lipid synthesis, protein synthesis). 

In skeletal muscle, glucose transport is non-equilibrium, so that an increase in activity of the transporter increases glucose utilisation. Factors that increase the activity of the transporter (e.g. the number of transporter molecules) in the membrane are insulin and sustained physical activity. In contrast, the hormone cortisol decreases the number of transporters in the membrane. This decreases glucose uptake and is one of the effects of cortisol that helps to maintain the normal blood glucose level (Chapter 12). 

Figure 6.15 Regulation of the number of glucose transporters in the plasma membrane. The transporter affected is GLUT-4. It is unclear which translocation process is affected by insulin, physical activity or a change in the ATP/ADP concentration ratio. Effects on the translocation from within the cell to the membrane or vice versa are indicated here.

Figure 6.19 Regulation of the synthesis of glycogen from glucose in liver and muscle. Insulin is the major factor stimulating glycogen synthesis in muscle it increases glucose transport into the muscle and the activity of glycogen synthase, activity which is also activated by glucose 6-phosphate but inhibited by glycogen. The latter represents a feedback mechanism and the former a feedforward. The mechanism by which glycogen inhibits the activity is not known. The mechanism for the insulin effect is discussed in Chapter 12.

Il.f.l.1. Insulins. Insulin is the most effective of diabetes medications. Insulin has profound effects on carbohydrate, protein, fat metabolism and electrolytes. It has anabolic and anticatabolic actions. In a state of insulin deficiency, glycogenesis, glucose transport, protein synthesis, triglyceride synthesis, LPL activity in adipose tissue, cellular potassium uptake all decrease on the other hand, gluconeogene-sis, glycogenolysis, protein degradation, ketogene-sis, lipolysis increase. 

Le Marchand-Brustel, Y. Heydrick, S.J. Jullien, D. Gautier, N. Van Ob-berghen, E. Effect of insulin and insulin-like growth factor-I on glucose transport and its transporters in soleus muscle of lean and obese mice. Metab. Clin. Exp., 44, 18-23 (1995)... 

The uptake of glucose by brain, liver, kidneys, erythrocytes, and the islets of Langerhans is unaffected by insulin. However, in muscle and adipose tissues insulin stimulates glucose uptake. Part of this effect results from insulin-induced translocation of molecules of the 509-residue glucose transport protein GLUT4 (Chapter 8) from the cytosol into the plasma membrane where it can function.354-3563 Insulin apparently also increases the rate of synthesis of the transporters. 

One of the most important effects of insulin is to increase glucose uptake by cells 373/389 The mechanism is thought to depend upon the transporter protein GLUT4, which is stored within the membranes of small cytoplasmic vesicles. Binding of insulin to its receptors induces movement of these vesicles to the plasma membrane where fusion with the plasma membrane makes the GLUT4 molecules available for glucose transport.390 Phosphatidylinositol 3-kinase also plays an important role. The PtdIns(3,4)P2 and PtdIns(3,4,5)P3 generated by this enzyme (Fig. 11-9)... 

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