For example, sustained or chronically elevated levels of ROS (i.e.: oxidative stress) have been implicated in insulin resistance via activation of stress activated protein kinases (SAPKs), which leads to insulin receptor substrate-1/2 (IRS1/2) serine phosphorylation, to negatively regulate phosphatidylinositol 3-kinase (PI3K) activity and its downstream signaling for GLUT-4 translocation and glucose uptake [18]. This evidence concerns the gene IRS1 and Insulin resistance.