@article{BaerFegerFajoletal.2018,
  author    = {B{\"a}r, Ludmilla and Feger, Martina and Fajol, Abul and Klotz, Lars-Oliver and Zeng, Shufei and Lang, Florian and Hocher, Berthold and F{\"o}ller, Michael},
  title     = {Insulin suppresses the production of fibroblast growth factor 23 (FGF23)},
  series = {Proceedings of the National Academy of Sciences of the United States of America},
  volume    = {115},
  journal   = {Proceedings of the National Academy of Sciences of the United States of America},
  number    = {22},
  publisher = {National Acad. of Sciences},
  address   = {Washington},
  issn      = {0027-8424},
  doi       = {10.1073/pnas.1800160115},
  pages     = {5804 -- 5809},
  year      = {2018},
  abstract  = {Fibroblast growth factor 23 (FGF23) is produced by bone cells and regulates renal phosphate and vitamin D metabolism, as well as causing left ventricular hypertrophy. FGF23 deficiency results in rapid aging, whereas high plasma FGF23 levels are found in several disorders, including kidney or cardiovascular diseases. Regulators of FGF23 production include parathyroid hormone (PTH), calcitriol, dietary phosphate, and inflammation. We report that insulin and insulin-like growth factor 1 (IGF1) are negative regulators of FGF23 production. In UMR106 osteoblast-like cells, insulin and IGF1 down-regulated FGF23 production by inhibiting the transcription factor forkhead box protein O1 (FOXO1) through phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB)/Akt signaling. Insulin deficiency caused a surge in the serum FGF23 concentration in mice, which was reversed by administration of insulin. In women, a highly significant negative correlation between FGF23 plasma concentration and increase in plasma insulin level following an oral glucose load was found. Our results provide strong evidence that insulin/IGF1dependent PI3K/PKB/Akt/FOXO1 signaling is a powerful suppressor of FGF23 production in vitro as well as in mice and in humans.},
  language  = {en}
}
@article{FegerFajolLebedevaetal.2013,
  author    = {Feger, Martina and Fajol, Abul and Lebedeva, Aleksandra and Meissner, Adrian and Michael, Diana and V{\"o}lkl, Jakob and Alesutan, Ioana and Schleicher, Erwin and Reichetzeder, Christoph and Hocher, Berthold and Qadri, Syed M. and Lang, Florian},
  title     = {Effect of Carbon Monoxide Donor CORM-2 on Vitamin D-3 Metabolism},
  series = {Kidney \& blood pressure research : official organ of the Gesellschaft f{\"u}r Nephrologie},
  volume    = {37},
  journal   = {Kidney \& blood pressure research : official organ of the Gesellschaft f{\"u}r Nephrologie},
  number    = {4-5},
  publisher = {Karger},
  address   = {Basel},
  issn      = {1420-4096},
  doi       = {10.1159/000355730},
  pages     = {496 -- 505},
  year      = {2013},
  abstract  = {Background/Aims: Carbon monoxide (CO) interferes with cytochrome-dependent cellular functions and acts as gaseous transmitter. CO is released from CO-releasing molecules (CORM) including tricarbonyl-dichlororuthenium (II) dimer (CORM-2), molecules considered for the treatment of several disorders including vascular dysfunction, inflammation, tissue ischemia and organ rejection. Cytochrome P450-sensitive function include formation of 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3) by renal 25-hydroxyvitamin D-3 1-alpha-hydroxylase (Cyp27b1). The enzyme is regulated by PTH, FGF23 and klotho. 1,25(OH)(2)D-3 regulates Ca2+ and phosphate transport as well as klotho expression. The present study explored, whether CORM-2 influences 1,25(OH)(2)D-3 formation and klotho expression. Methods: Mice were treated with intravenous CORM-2 (20 mg/kg body weight). Plasma 1,25(OH)(2)D-3 and FGF23 concentrations were determined by ELISA, phosphate, calcium and creatinine concentrations by colorimetric methods, transcript levels by quantitative RT-PCR and protein expression by western blotting. Fgf23 mRNA transcript levels were further determined in rat osteosarcoma UMR106 cells without or with prior treatment for 24 hours with 20 mu M CORM-2. Results: CORM-2 injection within 24 hours significantly increased FGF23 plasma levels and decreased 1,25(OH)(2)D-3 plasma levels, renal Cyp27b1 gene expression as well as renal klotho protein abundance and transcript levels. Moreover, treatment of UMR106 cells with CORM-2 significantly increased Fgf23 transcript levels. Conclusion: CO-releasing molecule CORM-2 enhances FGF23 expression and release and decreases klotho expression and 1,25(OH)(2)D-3 synthesis.},
  language  = {en}
}