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FGF-21 as a novel metabolic regulator

Journal of Clinical Investigation · 2005 · Vol. 115(6) · pp. 1627–1635
Alexei KharitonenkovTatiyana L. ShiyanovaAnja KöesterAmy FordRadmila MicanovicElizabeth J. GalbreathGeorge E. SanduskyLisa J. HammondJulie S. MoyersRebecca A. OwensJesper GromadaJoseph T. BrozinickEric D. HawkinsVictor J. WroblewskiDe-Shan LiFarrokh MehrbodS. Richard JaskunasArmen B. Shanafelt

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.

Fibroblast Growth Factor ResearchKruppel-like factors researchEpigenetics and DNA MethylationFGF21Fibroblast growth factorDiabetes mellitusRegulatorGenetically modified mouseEndocrinologyTransgeneObesityInternal medicineHypoglycemia

MeSH terms

AnimalsBlood GlucoseCell DivisionCells, CulturedDiabetes MellitusFibroblast Growth FactorsHumansHyperglycemiaHypoglycemic AgentsMice, ObeseMice, TransgenicTriglyceridesWeight GainAdipocytesMice

Funding

  • Eli Lilly and Company
  • Hospital for Sick Children
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