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- g1

L1 adipocytes (33,45-47), L6 muscle cells (48), and rat skeletal muscle (49). Further, specific inhibitors of PI-3 kinase inhibited insulin-stimulated glucose uptake in 3T3-L1 adipocytes (45) and a P85 mutant lacking the binding site J

Diabetes Sustenance

Diabetes Sustenance

Get All The Support And Guidance You Need To Be A Success At Dealing With Diabetes The Healthy Way. This Book Is One Of The Most Valuable Resources In The World When It Comes To Learning How Nutritional Supplements Can Control Sugar Levels.

Get My Free Ebook

Post a comment