FGF-21 as a novel metabolic regulator

Alexei Kharitonenkov(Eli Lilly (United States)), Tatiyana L. Shiyanova(Eli Lilly (United States)), Anja Köester(Eli Lilly (United States)), Amy Ford(Eli Lilly (United States)), Radmila Micanovic(Eli Lilly (United States)), Elizabeth J. Galbreath(Eli Lilly (United States)), George E. Sandusky(Eli Lilly (United States)), Lisa J. Hammond(Eli Lilly (United States)), Julie S. Moyers(Eli Lilly (United States)), Rebecca A. Owens(Eli Lilly (United States)), Jesper Gromada(Eli Lilly (United States)), Joseph T. Brozinick(Eli Lilly (United States)), Eric D. Hawkins(Eli Lilly (United States)), Victor J. Wroblewski(Eli Lilly (United States)), LI De-shan(Eli Lilly (United States)), Farrokh Mehrbod(Eli Lilly (United States)), S. Richard Jaskunas(Eli Lilly (United States)), Armen B. Shanafelt(Eli Lilly (United States))
Journal of Clinical Investigation
May 3, 2005
Cited by 2,078Open Access
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Abstract

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.


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