IRS1 and Insulin resistance: Chronic activation of mTOR/S6 kinase 1 (S6K1) by excessive nutrients, promotes insulin resistance in vascular through increased serine (Ser) phosphorylation (p) of the critical insulin signaling/docking molecule IRS-1, leading to impaired phosphoinositol 3 kinase (PI3-K) engagement and protein kinase B (Akt) stimulation, as well as reduced glucose transporter type 4 (GLUT4) translocation (Fig. 2).