Creatine feeding increases GLUT4 expression in rat skeletal muscle

Am J Physiol Endocrinol Metab. 2005 Feb;288(2):E347-52. doi: 10.1152/ajpendo.00238.2004. Epub 2004 Oct 19.


The purpose of this study was to investigate the potential role of creatine in GLUT4 gene expression in rat skeletal muscle. Female Wistar rats were fed normal rat chow (controls) or chow containing 2% creatine monohydrate ad libitum for 3 wk. GLUT4 protein levels of creatine-fed rats were significantly increased in extensor digitorum longus (EDL), triceps, and epitrochlearis muscles compared with muscles from controls (P < 0.05), and triceps GLUT4 mRNA levels were approximately 100% greater in triceps muscles from creatine-fed rats than in muscles from controls (P < 0.05). In epitrochlearis muscles from creatine-fed animals, glycogen content was approximately 40% greater (P < 0.05), and insulin-stimulated glucose transport rates were higher (P < 0.05) than in epitrochlearis muscles from controls. Despite no changes in [ATP], [creatine], [phosphocreatine], or [AMP], creatine feeding increased AMP-activated protein kinase (AMPK) phosphorylation by 50% in rat EDL muscle (P < 0.05). Creatinine content of EDL muscle was almost twofold higher for creatine-fed animals than for controls (P < 0.05). Creatine feeding increased protein levels of myocyte enhancer factor 2 (MEF2) isoforms MEF2A ( approximately 70%, P < 0.05), MEF2C ( approximately 60%, P < 0.05), and MEF2D ( approximately 90%, P < 0.05), which are transcription factors that regulate GLUT4 expression, in creatine-fed rat EDL muscle nuclear extracts. Electrophoretic mobility shift assay showed that DNA binding activity of MEF2 was increased by approximately 40% (P < 0.05) in creatine-fed rat EDL compared with controls. Our data suggest that creatine feeding enhances the nuclear content and DNA binding activity of MEF2 isoforms, which is concomitant with an increase in GLUT4 gene expression.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AMP-Activated Protein Kinases
  • Administration, Oral*
  • Animals
  • Creatine / administration & dosage*
  • DNA-Binding Proteins / metabolism*
  • Female
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Glucose / metabolism*
  • Glucose Transporter Type 4
  • MEF2 Transcription Factors
  • Monosaccharide Transport Proteins / biosynthesis*
  • Multienzyme Complexes / metabolism*
  • Muscle Proteins / biosynthesis*
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism*
  • Myogenic Regulatory Factors
  • Protein Serine-Threonine Kinases / metabolism*
  • Rats
  • Rats, Wistar
  • Transcription Factors / metabolism*


  • DNA-Binding Proteins
  • Glucose Transporter Type 4
  • MEF2 Transcription Factors
  • Monosaccharide Transport Proteins
  • Multienzyme Complexes
  • Muscle Proteins
  • Myogenic Regulatory Factors
  • Slc2a4 protein, rat
  • Transcription Factors
  • Protein Serine-Threonine Kinases
  • AMP-Activated Protein Kinases
  • Glucose
  • Creatine