Keap1, a component of an E3 ubiquitin ligase, precisely controls the transcription factor Nrf2 under homeostatic conditions by ubiquitination and proteasome-dependent destruction.392 This pathway has been extensively studied in cancer, chronic obstructive pulmonary disease, neurological diseases and autoimmune diseases, e.g., IBD and RA.393–395 However, the role of the antioxidant Nrf2/Keap1/ARE pathway in diabetic dysfunction was recently discovered, likely contributing to diabetes amputation.396. This evidence concerns the gene NFE2L2 and diabetes mellitus.