IRS1 and Insulin resistance: Defects in the canonical insulin signaling pathway that underlie pathological skeletal muscle insulin resistance can manifest through reduced phosphorylation of Insulin receptor substrate 1 (IRS1), Protein kinase B (AKT) (at Thr308), AKT substrate 160 (AS160), and decreased activity of Phosphoinositide 3‐kinases (PI3Ks) and glycogen synthase (Karlsson & Zierath, 2007).