Sirt1 Mediates Vitamin D Deficiency-Driven Gluconeogenesis in the Liver via mTorc2/Akt Signaling

Figure 3

1,25(OH)₂D₃ deficiency leads to increased gluconeogenesis and hepatic insulin resistance through impairing phosphorylation of AKT and phosphorylation of FOXO1. (a) ITT was performed in 6-month-old 1α(OH)ase^-/- and wild-type mice (). ns: not significant; blue line: RDWT group; red line: RDKO group; black bar: RDWT group; gray bar: RDKO group. (b, c) Insulin stimulated the phosphorylation of AKT-S473 and FOXO1-S256 in wild-type livers markedly but failed to do so in the mutant ones, as measured by Western blotting (b) and IHC (c). . ; magnification: 20x (c). (d) The phosphorylation of AKT-S473 and FOXO1-S256 was also inhibited in HepG2 cells transfected with si-VDR compared with HepG2 cells transfected with si-NC. . (e) Ectopic overexpression of FOXO1 increases transcriptional activity of PCK1 promoter. This effect was enhanced by knockdown of VDR. HepG2 cells were transfected with PCK1-luc, together with a FOXO1 expression vector (FOXO1) or a GFP expression vector as a control (GFP). , , .

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