FOXO1 and Insulin resistance: Reduced Sirt1 levels in 1α(OH)ase−/− mice downregulated the expression of Rictor, a key component of the mTorc2 complex, impaired the phosphorylation of AKT at S473 and FOXO1 at S256, and increased the expression of G6pase and PCK1, which resulted in hepatic glucose overproduction, hepatic insulin resistance, and, eventually, chronic hyperglycaemia.