Fibroblast growth factor FGF23, a powerful inhibitor of 1,25(OH)₂D₃ formation and renal phosphate reabsorption in the kidney, counteracts phosphate retention, vascular calcification and ageing. FGF23-deficient mice suffer from rapid aging and early death. Conversely, the life span is substantially increased in FGF23 overexpressing mice. Renal tubular phosphate transport is upregulated by insulin, an effect involving phosphatidylinositide (PI) 3 kinase (PI3 kinase) with subsequent activation of Akt and SGK as well as Akt/SGK dependent inhibition of GSK3. The present study tested the hypothesis, that insulin sensitive PI3 kinase signaling influences FGF23 expression. FGF23 transcript levels in rat osteosarcoma cell line (UMR106) were determined by RT-PCR, GSK3 phosphorylation in UMR106 cells by Western blotting. Plasma FGF23 and 1,25(OH)₂D₃ concentrations in mice carrying a PKB/SGK resistant GSK3a and GSK3b (gsk3^KI) and their corresponding wild type mice (gsk3^WT) were determined by EIA and ELISA, respectively. As a result, FGF23 transcript levels in UMR106 cells were increased by serum deprivation, an effect reversed by addition of insulin (100 nM), mimicked by pharmacological inhibition of PI3 kinase with Wortmannin (100 nM) and paralleled by increase of GSK3 phosphorylation. The transcript levels were significantly decreased by pharmacological inhibition of GSK3 with the specific GSK3 inhibitor SB216763 (10 mM). FGF23 plasma levels were significanty higher and 1,25(OH)₂D₃ plasma levels significantly lower in gsk^ki mice than in gsk3^WT mice. In conclusion, PI3K/PKB/SGK sensitive GSK3 inhibition participates in the regulation of FGF23 expression, FGF23 release 1,25(OH)₂D₃ formation and thus mineral metabolism.