Fig. 5

Overview of insulin regulation of major metabolic responses in the cells. Under physiological conditions, insulin binds to its receptor (IR) to enhance positive tyrosine IRS-1 phosphorylation, promoting the activation of PI3-K which in turn phosphorylates and activates p-Akt. High expression of p-Akt activates translocation of glucose transporter 4 and thus increasing glucose uptake by the cell. p-Akt also further phosphorylates GSK-3β, promoting the glucose storage as glycogen. Under pathophysiological conditions, oxidative stress and pro-inflammatory cytokines such as IL-6 enhance negative phosphorylation of IRS-1 ^{serine (307)}, causing insulin resistance. Activated NF-_KB activates serine/threonine kinases (JNK) which phosphorylates IRS-1 and also works via other pathways such as SOCS expression to inhibit the insulin signaling pathway