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  -