TY  - JOUR
A1  - Bär, Ludmilla
A1  - Feger, Martina
A1  - Fajol, Abul
A1  - Klotz, Lars-Oliver
A1  - Zeng, Shufei
A1  - Lang, Florian
A1  - Hocher, Berthold
A1  - Föller, Michael
T1  - Insulin suppresses the production of fibroblast growth factor 23 (FGF23)
JF  - Proceedings of the National Academy of Sciences of the United States of America
N2  - 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.
KW  - PI3K
KW  - PKB/Akt
KW  - Klotho
KW  - phosphate
Y1  - 2018
U6  - https://doi.org/10.1073/pnas.1800160115
SN  - 0027-8424
VL  - 115
IS  - 22
SP  - 5804
EP  - 5809
PB  - National Acad. of Sciences
CY  - Washington
ER  - 
TY  - JOUR
A1  - Glosse, Philipp
A1  - Feger, Martina
A1  - Mutig, Kerim
A1  - Chen, Hong
A1  - Hirche, Frank
A1  - Hasan, Ahmed Abdallah Abdalrahman Mohamed
A1  - Gaballa, Mohamed Mahmoud Salem Ahmed
A1  - Hocher, Berthold
A1  - Lang, Florian
A1  - Föller, Michael
T1  - AMP-activated kinase is a regulator of fibroblast growth factor 23 production
JF  - Kidney international : official journal of the International Society of Nephrology
N2  - Fibroblast growth factor 23 (FGF23) is a proteohormone regulating renal phosphate transport and vitamin D metabolism as well as inducing left heart hypertrophy. FGF23-deficient mice suffer from severe tissue calcification, accelerated aging and a myriad of aging-associated diseases. Bone cells produce FGF23 upon store-operated calcium ion entry (SOCE) through the calcium selective ion channel Orai1. AMP-activated kinase (AMPK) is a powerful energy sensor helping cells survive states of energy deficiency, and AMPK down-regulates Orai1. Here we investigated the role of AMPK in FGF23 production. Fgf23 gene transcription was analyzed by qRT-PCR and SOCE by fluorescence optics in UMR106 osteoblast-like cells while the serum FGF23 concentration and phosphate metabolism were assessed in AMPKa1-knockout and wild-type mice. The AMPK activator, 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) down-regulated, whereas the AMPK inhibitor, dorsomorphin dihydrochloride (compound C) and AMPK gene silencing induced Fgf23 transcription. AICAR decreased membrane abundance of Orai1 and SOCE. SOCE inhibitors lowered Fgf23 gene expression induced by AMPK inhibition. AMPKa1-knockout mice had a higher serum FGF23 concentration compared to wild-type mice. Thus, AMPK participates in the regulation of FGF23 production in vitro and in vivo. The inhibitory effect of AMPK on FGF23 production is at least in part mediated by Orai1-involving SOCE.
KW  - calcium
KW  - FGF23
KW  - Klotho
KW  - Orai1
KW  - phosphate
KW  - parathyroid hormone
Y1  - 2018
U6  - https://doi.org/10.1016/j.kint.2018.03.006
SN  - 0085-2538
SN  - 1523-1755
VL  - 94
IS  - 3
SP  - 491
EP  - 501
PB  - Elsevier
CY  - New York
ER  - 
TY  - CHAP
A1  - Chen, Hong
A1  - Reichetzeder, Christoph
A1  - Föller, Michael
A1  - Slowinski, Torsten
A1  - Li, Jian
A1  - Chen, You-Peng
A1  - Lang, Florian
A1  - Hocher, Berthold
T1  - Maternal vitamin D deficiency and fetal programming
T2  - Acta physiologica : official journal of the Federation of European Physiological Societies
Y1  - 2015
SN  - 1748-1708
SN  - 1748-1716
VL  - 213
SP  - 155
EP  - 156
PB  - Wiley-Blackwell
CY  - Hoboken
ER  -