IRS1 and Insulin resistance: For example, TNF-activated signaling molecules such as IKK, JNK, S6 kinase, and mammalian target of rapamycin (mTOR) could potentially phosphorylate insulin receptor substrate 1 (IRS1) to attenuate insulin signaling and subsequently contribute to the development of insulin resistance (Gao et al., 2002; Gao et al., 2003; Hirosumi et al., 2002; Lee et al., 2007; Ozes et al., 2001; Yin et al., 1998).