Oxidative stress can damage insulin sensitivity and lead to insulin resistance and cognitive dysfunction of diabetes by downregulating the proteins involved in normal IST, such as Insulin-degrading enzyme (IDE), Biliverdin reductase-A (BVR-A), Akt, IRS, IRS-1 and GSK-3 (48, 83, 50). The gene discussed is INS; the disease is Insulin resistance.