IRS1 and Insulin resistance: TNF-α promotes insulin resistance by reducing insulin-mediated tyrosine phosphorylation of the insulin receptor (IR) and by inhibiting the tyrosine kinase activity of IR via serine phosphorylation of IRS-1 [133,140]; it also inhibits the activity of phosphatidylinositol 3-kinase (PI-3 kinase) [141], the autophosphorylation of IR, and the subsequent translocation of GLUT4 to the plasma membrane [142].