IRS1 and Insulin resistance: Pro-inflammatory cytokines secreted in the adipose tissue and by macrophages such as tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and IL-6 can promote insulin resistance by multiple mechanisms [85,86], which include Ser/Thr kinase activation and decreases in IRS-1, glucose transporter type 4 (GLUT-4), and peroxisome proliferator-activated receptor gamma (PPARγ) expression or suppressor of cytokine signaling 3 (SOCS-3) activation [63,87,88,89].