Insulin suppresses the production of fibroblast growth factor 23 (FGF23).

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/IGF1-dependent PI3K/PKB/Akt/FOXO1 signaling is a powerful suppressor of FGF23 production in vitro as well as in mice and in humans.

• Authors: Ludmilla Bär, Martina Feger, Abul Fajol, Lars-Oliver Klotz, Shufei Zeng, Florian Lang, Berthold Hocher, Michael Föller
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 115 Issue 22 Pg. 5804-5809 (05 29 2018) ISSN: 1091-6490 [Electronic] United States
• PMID: 29760049 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• FGF23 protein, human
• Fgf23 protein, mouse
• Insulin
• Fibroblast Growth Factors
• Fibroblast Growth Factor-23
• Proto-Oncogene Proteins c-akt
• Glucuronidase
• Klotho Proteins
• Glucose

Topics

• Animals
• Cell Line, Tumor
• Diabetes Mellitus, Experimental (metabolism)
• Female
• Fibroblast Growth Factor-23
• Fibroblast Growth Factors (blood, metabolism)
• Gene Expression Regulation (physiology)
• Glucose (administration & dosage, metabolism)
• Glucuronidase (metabolism)
• Humans
• Insulin (blood, metabolism, physiology)
• Klotho Proteins
• Male
• Mice
• Phosphatidylinositol 3-Kinases (metabolism)
• Pregnancy
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats
• Signal Transduction (physiology)