HMOX1 and Hyperglycemia: Nrf2 is rapidly up‐regulated in response to hyperglycemia stress and then translocates to the nucleus to increase the transcription of oxidative stress response genes, such as HO‐1, NQO‐1 and CAT. 38Moreover, several studies have demonstrated that Nrf2 may be up‐regulated by activation of AKT and GSK‐3β,39, 40, 41 and the nuclear translocation of Nrf2 requires the activation of the PI3K/AKT pathway.42, 43