INSR and Insulin resistance: Proinflammatory cytokines can directly induce insulin resistance through different mechanisms, including a reduction in the number and catalytic activity of insulin receptors, an increase in Ser/Thr phosphorylation of insulin receptor and IRS, an increase in tyrosine phosphatase activity, primarily PTP-1B, which participates in receptor and IRS dephosphorylation, a decrease in PI3K and Akt kinase activity, and defects in GLUT-4 expression and function20,22.