Glucose transporters translocation

Cheatham, B., Vlahos, C. J., Cheatham, L., Wang, L., Blenis, J., and Kahn, C. R. (1994). Phosphatidylinositol 3-kinase activation is required for insulin stimulation of pp70 S6 kinase, DNA synthesis, and glucose transporter translocation. Mol. Cell. Biol. 14, 4902-4911. 

Simulation of glucose transport and glucose transporter translocation from intracellular stores to the plasma membrane in muscle cells by vanadate and peroxovan-adate involve a mechanism independent of PI-3K and protein kinase C systems utilized for stimulation of these processes by insulin. The transport of GLUT4 to the plasma membrane in muscle cells growing in culture after stimulation by vanadate, peroxovanadate, or insulin all require an intact actin network [138], Sometimes, the insulin-like action of vanadium is accompanied by overall stimulation of actual metabolic pathways. One example of this is the stimulation of the pentose phosphate pathway observed when vanadate promotes the incorporation of glucose into lipids, an antilipogenic effect [139],... 

G. Muller and S. Wied, The sulfonylurea drug, ghmepiride, stimulates glucose transport, glucose transporter translocation, and dephosphorylation in insulin-resistant rat adipocytes in vitro. Diabetes,... 

Fat Increased glucose transport GLUT4-translocation PI 3-kinase/Akt mediated translocation of GLUT4 into the plasma membrane. Potential involvement of atypical forms of protein kinase C (PKC and A)... 

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

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.

Activation of a protein kinase that is responsible for many of the metabolic effects, for example increased activity of glycogen synthase, increased translocation of the glucose transporter molecules to the plasma membrane and increased activity of acetyl-CoA carboxylase. 

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. 

Bazuine M, Ouwens DM Gomes de Mesquita DS, Maassen JA. 2003. Arsenite stimulated glucose transport in 3T3-L1 adipocytes involves both Glut4 translocation and p38 MAPK activity. Eur J Biochem 270 3891-3903. 

Tsiani, E., E. Bogdanovic, A. Sorisky, L. Nagy, and I.G. Fantus. 1998. Tyrosine phosphatase inhibitors, vanadate and pervanadate, stimulate glucose transport and GLUT translocation in muscle cells by a mechanism independent of phosphatidyli-nositol 3-kinase and protein kinase C. Diabetes 47 1676-1686. 

Sweeney, G., Keen, J., Somwar, R., Konrad, D., Garg, R., and Klip, A. 2001. High leptin levels acutely inhibit insulin-stimulated glucose uptake without affecting glucose transporter 4 translocation in 16 rat skeletal muscle cells. Endocrinology 142 4806-4812. 

The primary, secondary, and presumably tertiary, and higher, structure of the family of facilitative glucose transporters are similar. It is beginning to be understood which domains of these transporters are important for substrate and inhibitor binding and for subcellular localization. Future work will undoubtably uncover the molecular mechanism by which the facilitative transporters catalyze the translocation of sugars across the membrane. 

It has now been generally accepted that a major mechanism for the regulation of Na+-independent glucose transport activity in insulin responsive adipose tissue and muscle is by the translocation of transporters from a cytoplasmic pool (Cushman and Wardzala, 1980 Suzuki and Kono, 1980). 

Cushman, S.W. Wardzala, L.J. (1980). Potential mechanism of insulin action on glucose transport in the isolated rat adipose cell. Apparent translocation of intracellular transport systems to the plasma membrane. J. Biol. Chem. 255,4758-4762. 

Suzuki, K. Kono, T. (1980). Evidence that insulin causes translocation of glucose transport activity to the plasma membrane from an intracellular storage site. Proc. Natl. Acad. Sci. USA 77, 2542-2545. 

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