IRS1 and Hyperglycemia: ROS which could be augmented by hyperglycemia activate proinflammatory pathways including IKKβ and JNK which subsequently phosphorylate inhibitory sites such as Ser307 of IRS-1 (Ozes et al., 2001; Gao et al., 2002; Bloch-Damti and Bashan, 2005; Kamata et al., 2005).