Figure 2. Insulin signaling pathway.
After insulin binds to its receptor IR, the receptor phosphorylates and activates IRS-1. Akt is activated by PI3K/PDK-1 and, in turn, activates several metabolic pathways, including GLUT4 translocation. Following chronic insulin stimulation, mTOR, through the activation of p70S6K (S6K), inhibits PI3K signaling by promoting reduction in IRS-1 stability and transcription, leading to its de-association from PI3K (negative-feedback regulation). In addition, S6K can phosphorylate IRS-1 on multiple inhibitory sites, promoting its degradation.
aPKC: Atypical protein kinase C; GLUT4: Glucose transporter-4; IR: Insulin receptor; PDK-1: Phosphoinositide-dependent protein kinase 1; PIP2: Phosphatidylinositol 4,5-bisphosphate; PIP3: Phosphatidylinositol 3,4,5-triphosphate.
