By understanding how 1,25(OH)2D3 deletion stimulates G6PC and PCK1 transcription through suppression of the Sirt1-mTOR2/AKT/FOXO1 axis and determining the role of Sirt1 in VD deficiency-induced impairment of insulin sensitivity and glucose intolerance, we provide critical evidence about a significant metabolic pathway involved in the type 2 diabetes. This evidence concerns the gene FOXO1 and type 2 diabetes mellitus.