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PMID: 15902306 Published · ppublish English Journal Article

FGF-21 as a novel metabolic regulator.

The Journal of clinical investigation ·Vol. 115 ·No. 6 ·2005-06-00 ·Pages 1627-35

Kharitonenkov A, Shiyanova TL, Koester A, Ford AM, Micanovic R, Galbreath EJ, Sandusky GE, Hammond LJ, Moyers JS, Owens RA, Gromada J, Brozinick JT, Hawkins ED, Wroblewski VJ, Li DS, Mehrbod F, Jaskunas SR, Shanafelt AB

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.

MeSH Terms
Adipocytes/cytology,metabolism Animals Blood Glucose/analysis Cell Division/drug effects Cells, Cultured Diabetes Mellitus/blood,drug therapy,pathology Fibroblast Growth Factors/administration & dosage,genetics,metabolism Humans Hyperglycemia/blood,genetics,metabolism,pathology Hypoglycemic Agents/administration & dosage,metabolism Mice Mice, Obese Mice, Transgenic Triglycerides/blood Weight Gain/drug effects,genetics
Chemicals
Blood Glucose Hypoglycemic Agents Triglycerides fibroblast growth factor 21 Fibroblast Growth Factors
Authors & Affiliations
18 authors, click to expand affiliations / ORCID
Kharitonenkov Alexei
Lilly Research Laboratories, Division of Eli Lilly and Co., Indianapolis, Indiana 46285, USA. a.kharch@lilly.com
Shiyanova Tatiyana L
Koester Anja
Ford Amy M
Micanovic Radmila
Galbreath Elizabeth J
Sandusky George E
Hammond Lisa J
Moyers Julie S
Owens Rebecca A
Gromada Jesper
Brozinick Joseph T
Hawkins Eric D
Wroblewski Victor J
Li De-Shan
Mehrbod Farrokh
Jaskunas S Richard
Shanafelt Armen B
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI23606
Email
a.kharch@lilly.com
Published
2005-06-00
Epub
2005-00-02
Pages
1627-35
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC1088017
Subset
IM
External Links
PubMed source DOI: 10.1172/JCI23606 PMC Full Text View journal details
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