GLUT-4 translocation

GLUT 4 translocation to the cell membrane in skeletal muscle is stimulated by exercise. This effect, which is independent of insulin, involves a 5 AMP-activated kinase. 

GLUT-4 translocation to the plasma membrane enhances glucose uptake into the myocyte in the first few minutes of light exercise. 

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. 

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.

Stimulated translocation of the GLUT-4 glucose transporter (which is regulated by insulin) to the plasma membrane was demonstrated in rat adipocytes, and increased glucose transporter expression in the presence of vanadate was shown in vitro in NIH 3T3 mouse fibroblasts and in vivo in rat skeletal muscle. Vanadate increased sensitivity to insulin in activating glucose transport in normal and insulin-resistant rat adipocytes (but not human adipocytes ), via enhanced insulin binding. 

Most members of classes II aud in have beeu ideutified iu geuomewide database searches. The fuuctiou of these newly discovered transporter isoforms is not yet well defined. Several of them (GLUT-6 and 8) contain motifs that lead to their retention inside the cell, and therefore this prevents their involvement in glucose transport at the plasma membrane. Whetho" mechanisms exist to invoke ceU surface insafion of these transporta is unknown, but it has been established that insulin does not promote translocation of GLUT-6 and GLUT-8 to the ceU surface. 

Glucose transport across membranes occurs via a transporter protein, i.e. GLUT transporters. These transmembrane proteins bind glucose on one face of the membrane, then undergo conformational change to translocate glucose across the membrane. The different types of GLUT transporter are oudined in the table... 

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