IRS1 and Insulin resistance: Moreover, ROS have been proposed to contribute to insulin resistance (IR) itself: activation of stress-activated protein kinases by ROS can lead to impairment of the correct transduction of insulin-mediated signals through the induction of serine and threonine phosphorylation of IRS-1 (insulin receptor substrate-1) and the concomitant down-regulation of IRS-1 tyrosine phosphorylation [157,158].