INS and Hyperglycemia: As the secretion and action of insulin are controlled by a molecular pathway called as insulin signaling cascade, hyperglycemia-induced oxidative stress could decrease ATP/ADP ratio and disturb the normal Na+-K+ ratio, which causes a depolarization of the membrane and more influx of Ca2+, accelerates the decomposition of membrane phospholipids and damages pancreatic cells (Newsholme et al., 2016).