ROS action is generally beneficial. However, under diabetic conditions, chronic hyperglycemia and consequent augmentation of reactive oxygen species (ROS) deteriorate beta-cell function and escalate insulin resistance. This leads to an aggravation of type 2 diabetes. Additionally, chronic hyperglycemia and ROS are also involved in the development of atherosclerosis which is often observed under diabetic conditions.
Such disturbances contribute to the pathogenesis of various diseases, including diabetes. To counteract these insults, most cells, including β-cells, have intricate mechanisms of defense against ROS toxicity. Among these, the transcription factor NF-E2–related factor 2 (Nrf2) is a pivotal component for protecting cells from oxidative damage.
In response to oxidative stress, activation of Nrf2 dramatically increases intracellular antioxidant potential by directly increasing the transcription of many so-called antioxidant enzymes. Thus, the Nrf2-mediated induction of antioxidant enzymes is critically important for proper oxidation/reduction (redox) homeostasis to protect cells from irreversible oxidative damage.