NKX6-1 and Hyperglycemia: Downregulation of FOXO1 may be caused by chronic hyperglycemia‐induced oxidative stress; consequently, β‐cell fate cannot be maintained, due to insufficient β‐cell transcription factors, PDX1, MAFA, and NKX6.1, all of which are FOXO1‐dependent (Kitamura et al., 2005).