Farnesoid X receptor induces GLUT4 expression through FXR response element in the GLUT4 promoter

Cell Physiol Biochem. 2008;22(1-4):1-14. doi: 10.1159/000149779. Epub 2008 Jul 25.


GLUT4, the main insulin-responsive glucose transporter, plays a critical role in maintaining systemic glucose homeostasis and is subject to complicated metabolic regulation. GLUT4 expression disorder might cause insulin resistance, and over-expression of GLUT4 has been confirmed to ameliorate diabetes. Here, we reported that farnesoid X receptor (FXR) and its agonist chenodeoxycholic acid (CDCA) could induce GLUT4 transcription in 3T3-L1 and HepG2 cells. Furthermore, CDCA could increase the GLUT4 protein amount in C57BL/6J mice sex-dependently. The following progressive 5'-deletion analysis and site-mutation investigation further suggested that FXR could induce GLUT4 expression through FXR response element (FXRE) in the GLUT4 promoter. EMSA and knock-down of retinoid X receptor (RXR) indicated that FXR binds to the GLUT4-FXRE as a monomer and RXR does not participate in the FXR stimulation of GLUT4 expression. In addition, we demonstrated that FXR does not interfere with insulin-induced GLUT4 translocation to plasma membrane. All these data thereby implied that FXR is a new transcription factor of GLUT4, further elucidating the potential role for FXR in glucose metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Animals
  • Base Sequence
  • Binding Sites
  • Cell Line, Tumor
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Chenodeoxycholic Acid / pharmacology
  • DNA-Binding Proteins / agonists
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism*
  • Electrophoretic Mobility Shift Assay
  • Female
  • Gene Expression Regulation / drug effects
  • Glucose Transporter Type 4 / genetics*
  • Glucose Transporter Type 4 / metabolism
  • Humans
  • Insulin / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • PPAR gamma / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Binding / drug effects
  • Protein Conformation
  • Protein Transport / drug effects
  • Receptors, Cytoplasmic and Nuclear / agonists
  • Receptors, Cytoplasmic and Nuclear / chemistry
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Response Elements / genetics*
  • Retinoid X Receptors / metabolism
  • Sex Characteristics
  • Transcription Factors / agonists
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism*


  • DNA-Binding Proteins
  • Glucose Transporter Type 4
  • Insulin
  • PPAR gamma
  • Receptors, Cytoplasmic and Nuclear
  • Retinoid X Receptors
  • Transcription Factors
  • farnesoid X-activated receptor
  • Chenodeoxycholic Acid
  • Phosphatidylinositol 3-Kinases