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

Figure 7

Model of mechanisms leading from 1,25(OH)₂D₃ deficiency to increased hepatic gluconeogenesis. 1,25(OH)₂D₃-mediated pathway and insulin-mediated pathway converge on AKT, working together to promote AKT phosphorylation at Ser473 and then FOXO1 phosphorylation at Ser256. 1,25(OH)₂D₃ deficiency suppresses Sirt1 expression, leading to downregulation of Rictor which further impaired phosphorylation of AKT-S473 and FOXO1-S256. As a result, the expression of G6Pase and PCK1 is upregulated, causing hepatic glucose overproduction and hepatic insulin resistance.