IRS1 and Insulin resistance: TZDs act as ligands, and activation of PPARγ upregulates genes related to the glucose metabolism pathway (including GLUT4, IRS-1, IRS-2, and c-Cbl associated protein) and insulin-sensitizing adipokine gene expression (lipocalin) and downregulates the expression of cytokine genes involved in the induction of insulin resistance (tumor necrosis factor-α [TNF-α] and interleukin-6 [IL-6]), thereby regulating blood glucose levels [124,125].