FGF-21 as a novel metabolic regulator

Alexei Kharitonenkov, Tatiyana L. Shiyanova, Anja Koester, Amy M. Ford, Radmila Micanovic, Elizabeth J. Galbreath, George E. Sandusky, Lisa J. Hammond, Julie S. Moyers, Rebecca A. Owens, Jesper Gromada, Joseph T. Brozinick, Eric D. Hawkins, Victor J. Wroblewski, De Shan Li, Farrokh Mehrbod, S. Richard Jaskunas, Armen B. Shanafelt

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1281 Scopus citations


Diabetes mellitus is a major health concern, affecting more than 5% of the population. Here we describe a potential novel therapeutic agent for this disease, FGF-21, which was discovered to be a potent regulator of glucose uptake in mouse 3T3-L1 and primary human adipocytes. FGF-21-transgenic mice were viable and resistant to diet-induced obesity. Therapeutic administration of FGF-21 reduced plasma glucose and triglycerides to near normal levels in both ob/ob and db/db mice. These effects persisted for at least 24 hours following the cessation of FGF-21 administration. Importantly, FGF-21 did not induce mitogenicity, hypoglycemia, or weight gain at any dose tested in diabetic or healthy animals or when overexpressed in transgenic mice. Thus, we conclude that FGF-21, which we have identified as a novel metabolic factor, exhibits the therapeutic characteristics necessary for an effective treatment of diabetes.

Original languageEnglish (US)
Pages (from-to)1627-1635
Number of pages9
JournalJournal of Clinical Investigation
Issue number6
StatePublished - Jun 1 2005
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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    Kharitonenkov, A., Shiyanova, T. L., Koester, A., Ford, A. M., Micanovic, R., Galbreath, E. J., Sandusky, G. E., Hammond, L. J., Moyers, J. S., Owens, R. A., Gromada, J., Brozinick, J. T., Hawkins, E. D., Wroblewski, V. J., Li, D. S., Mehrbod, F., Jaskunas, S. R., & Shanafelt, A. B. (2005). FGF-21 as a novel metabolic regulator. Journal of Clinical Investigation, 115(6), 1627-1635. https://doi.org/10.1172/JCI23606