Insulin Stimulated Glucose Transport

The generation of the second messengers following insulin receptor binding and activation promotes cellular glucose transport into the cell. The enhanced insulin-stimulated glucose transport is mediated by translocation of a large number of glucose transporters from an intracellular pool to the plasma membrane (42). The glucose transporters consist of at least five homologous transmembrane proteins (Glut-1, -2, -3, -4, and -5) encoded by distinct genes, and have distinct specificities, kinetic properties, and tissue distribution that define their clinical role (42). Glut-1 and Glut-4 are two major glucose transporters that have been identified in skeletal muscle. Whereas Glut-1 may be primarily involved in basal glucose uptake, Glut-4 is considered the major insulin-responsive glucose transporter. In addition to skeletal muscle, Glut-4 is expressed in insulin target tissues such as cardiac muscle and adipose tissue. In normal muscle cells, Glut-4 is recycled between the plasma membrane and intracellular storage pools; thus it differs from other transporters in that approximately 90% of it is sequestered intracellularly in the absence of insulin (42). With stimulation by insulin, the equilibrium of this recycling process is altered to favor translocation (regulated movement) of Glut-4 from intracellular stores to the plasma membrane and transverse tubules in the muscle, resulting in a rise in the maximal velocity of glucose transport into the cell (42).

As outlined, cellular trafficking of Glut-4 in insulin-sensitive tissues follows insulin receptor binding and activation of tyrosine kinase phosphorylation at the intracellular portion of the receptor. In addition, subsequent activation of PI-3 kinase by insulin-stimulated IRS phosphorylation appears to be a necessary -o step for glucose transport (33-36), glycogen synthesis (37), and Glut-4 transloca- |

tion (34,40-43). Specifically, activation of PI-3 kinase has been reported to be £

necessary for insulin-stimulated glucose uptake in rat adipocytes (34,44), 3T3- g

L1 adipocytes (33,45-47), L6 muscle cells (48), and rat skeletal muscle (49). <j

Further, specific inhibitors of PI-3 kinase inhibited insulin-stimulated glucose Ja uptake in 3T3-L1 adipocytes (45) and a P85 mutant lacking the binding site J

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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