NFE2L2 and Hyperglycemia: In particular, hyperglycemia initiates an early increase of reactive oxygen species (ROS), which triggers the activation of endogenous antioxidant response through increased levels of nuclear factor erythroid 2-related factor 2 (Nrf2) leading to the transcription of antioxidant enzymes such as heme oxygenase-1 (HO-1) (Kang and Yang, 2020).