TNF-α promotes insulin resistance through downstream alternative phosphorylation of the insulin receptor (IR) docking protein, insulin receptor substrate-1 (IRS-1) (Peraldi et al. 1996), which prevents phosphorylation of protein kinase B (Akt) (Thong et al. 2005) and impairs transport of glucose transporter type 4 vesicles in skeletal muscle and adipose tissue to the plasma membrane (Peraldi and Spiegelman 1998). Here, IRS1 is linked to Insulin resistance.