Under IR conditions, hyperglycemia plays a significant role in inducing Nrf2 degradation in the liver by upregulating Keap1 or through activating other non-Keap1 degradation pathways such as glycogen synthase kinase 3 (GSK3), which induces phosphorylation-mediated degradation of Nrf2 [80]. This evidence concerns the gene NFE2L2 and Hyperglycemia.