FGF-21 as a Novel Metabolic Regulator

J Clin Invest. 2005 Jun;115(6):1627-35. doi: 10.1172/JCI23606. Epub 2005 May 2.

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
  • Adipocytes / metabolism
  • Animals
  • Blood Glucose / analysis
  • Cell Division / drug effects
  • Cells, Cultured
  • Diabetes Mellitus / blood
  • Diabetes Mellitus / drug therapy*
  • Diabetes Mellitus / pathology
  • Fibroblast Growth Factors / administration & dosage*
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / metabolism
  • Humans
  • Hyperglycemia / blood
  • Hyperglycemia / genetics
  • Hyperglycemia / metabolism
  • Hyperglycemia / pathology
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / metabolism
  • Mice
  • Mice, Obese
  • Mice, Transgenic
  • Triglycerides / blood
  • Weight Gain / drug effects
  • Weight Gain / genetics

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Triglycerides
  • fibroblast growth factor 21
  • Fibroblast Growth Factors