INS and Insulin resistance: Although multiple factors are attributed to the development of skeletal muscle insulin resistance including defective glucose and lipid utilization [18], progressive mitochondrial decline [19], aging [20], and oxidative stress [21], a key feature is the impairment of the canonical (PI3K/AKT) [22,23] and non-canonical (GTPase/Actin remodeling) insulin signaling cascades [24].