Glucose transporter skeletal muscle

The absorption of sulfonylureas from the upper gastrointestinal tract is faidy rapid and complete. The agents are transported in the blood as protein-bound complexes. As they are released from protein-binding sites, the free (unbound) form becomes available for diffusion into tissues and to sites of action. Specific receptors are present on pancreatic islet P-ceU surfaces which bind sulfonylureas with high affinity. Binding of sulfonylureas to these receptors appears to be coupled to an ATP-sensitive channel to stimulate insulin secretion. These agents may also potentiate insulin-stimulated glucose transport in adipose tissue and skeletal muscle. 

Skeletal muscle Increased glucose transport GLUT4-translocation see above (fat)... 

The entry rate of glucose into red blood cells is far greater than would be calculated for simple diffusion. Rather, it is an example of facilitated diffiision (Chapter 41). The specific protein involved in this process is called the glucose transporter or glucose permease. Some of its properties are summarized in Table 52-3-The process of entry of glucose into red blood cells is of major importance because it is the major fuel supply for these cells. About seven different but related glucose transporters have been isolated from various tissues unlike the red cell transporter, some of these are insidin-dependent (eg, in muscle and adipose tissue). There is considerable interest in the latter types of transporter because defects in their recruitment from intracellular sites to the surface of skeletal muscle cells may help explain the insulin resistance displayed by patients with type 2 diabetes mellitus. 

Fukumoto, H., et al. Cloning and characterization of the major insulin-responsive glucose transporter expressed in human skeletal muscle and other insulin-responsive tissues. J. Biol. Chem. 1989, 264, 7776-7779. 

Doege, H., et al. Characterization of human glucose transporter (GLUT) 11 (encoded by SLC2A11), a novel sugar-transport facilitator specifically expressed in heart and skeletal muscle. Biochem. J. 2001, 359, 443-449. 

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 6.14 An increase in the rate of glucose transport, in response to insulin, which increases the rate of glycolysis. This is achieved by increasing the concentrations of all the intermediates in the pathway, indicated by the arrows adjacent to the intermediates. Insulin, physical activity or a decrease in the ATP/ADP concentration ratio all result in increased rates of glucose transport in skeletal muscle. Insulin increases the rate about fivefold, physical activity about 50-fold.

Glucose transport into skeletal muscle cells via insulin-dependent glucose transport proteins in the plasma membrane (see p. 95) and subsequent glucose metabolism are depressed because of low levels of circulating insulin. 

Pereira LO, Lancha AH Jr. Effect of insulin and contraction up on glucose transport in skeletal muscle. Prog Biophys Mol Biol. 2004 84 1-27. 

Weinstein, S. P., Holand, A., O Boyle, E., and Haber, R. S. (1993). Effects of Thia-zolidinediones on Glucocorticoid-Induced Insulin Resistance and GLUT4 Glucose Transporter Expression in Rat Skeletal Muscle. Metabolism 42, 1365-1369. 

Hajduch E, Rencurel F, Balendran A, Batty IH, Downes CP, Hundal HS. Serotonin (5-hydroxytryptamine), a novel regulator of glucose transport in rat skeletal muscle. J Biol Chem 1999 274 13,563-13,568. 

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