Figure 1.

Schematic diagram of inactivation of β‐cell transcriptional factors in the development of diabetes. (a) Nuclear localization of forkhead box O1 (FOXO1) is the initial step in the maladaptation of β cells. (b) Sustained hyperglycemia or oxidative stress induces dephosphorylation, dimerization, translocation to the cytoplasm and loss of musculoaponeurotic fibrosarcoma oncogene family A (MAFA). (c) This behavior of might also be applicable to MAFB in human β‐cells. Reduction of nuclear NK transcription factor‐related, gene family 6, locus 1 (NKX6.1) is the next step of β‐cell failure. (d) Finally, the contents of pancreatic duodenal homeobox 1 (PDX1) and FOXO1 are diminished, causing further impairment of insulin production, reduction of the β‐cell mass, and overt diabetes.