Inhibition of PI3K blocks GLUT4 translocation while over exp

Inhibition of PI3K blocks GLUT4 translocation while over expression of PI3k promotes GLUT4 translocation. in your own words, describe why the authors suggest that there must be a second pathway downstream of the insulin receptor that is essential to GLUT4 translocation to occur.

Solution

It is known that both activation of PI3-kinase and production of 3\'-phosphoinositides through the IRS signaling pathway is required for insulin stimulated GLUT4 translocation.While activation of integrin receptor signaling induces PI3K to generate PI3,4,5P3 production in adipocytes but that does not promote GLUT4 translocation.Also it has be found through research that analog of PI3 alone also do not stimulate glucose uptake when added to cells but presence of wortmannin that blocks the activity of PI3 kinase activity, the addition of PI3 analog together with insulin resulted in GLUT4 translocation.Further studies have revealed that the PI3 analogs induced GLUT4 translocation but GLUT4 was not functioning which suggested that there must be a PI3K independent glucose transport activation pathway.These outcomes probably make the authors suggest there must be a second pathway downstream of the insulin receptor that is essential to GLUT4 translocation to occur. This second pathway is triggered by a substrate for insulin receptor tyrosine kinase known as Cbl .Cbl and IRS-PI 3-kinase signaling pathway work together jointly.