Creatine supplementation increases glucose oxidation and AMPK phosphorylation and reduces lactate production in L6 rat skeletal muscle cells

J Physiol. 2004 Mar 1;555(Pt 2):409-21. doi: 10.1113/jphysiol.2003.056291. Epub 2004 Jan 14.


Recent observations have suggested that creatine supplementation might have a beneficial effect on glucoregulation in skeletal muscle. However, conclusive studies on the direct effects of creatine on glucose uptake and metabolism are lacking. The objective of this study was to investigate the effects of creatine supplementation on basal and insulin-stimulated glucose transporter (GLUT4) translocation, glucose uptake, glycogen content, glycogen synthesis, lactate production, glucose oxidation and AMP-activated protein kinase (AMPK) phosphorylation in L6 rat skeletal muscle cells. Four treatment groups were studied: control, insulin (100 nM), creatine (0.5 mM) and creatine + insulin. After 48 h of creatine supplementation the creatine and phosphocreatine contents of L6 myoblasts increased by approximately 9.3- and approximately 5.1-fold, respectively, but the ATP content of the cells was not affected. Insulin significantly increased 2-deoxyglucose uptake ( approximately 1.9-fold), GLUT4 translocation ( approximately 1.8-fold), the incorporation of D-[U-(14)C]glucose into glycogen ( approximately 2.3-fold), lactate production ( approximately 1.5-fold) and (14)CO(2) production ( approximately 1.5-fold). Creatine neither altered the glycogen and GLUT4 contents of the cells nor the insulin-stimulated rates of 2-DG uptake, GLUT4 translocation, glycogen synthesis and glucose oxidation. However, creatine significantly reduced by approximately 42% the basal rate of lactate production and increased by approximately 40% the basal rate of (14)CO(2) production. This is in agreement with the approximately 35% increase in citrate synthase activity and also with the approximately 2-fold increase in the phosphorylation of both alpha-1 and alpha-2 isoforms of AMPK after creatine supplementation. We conclude that 48 h of creatine supplementation does not alter insulin-stimulated glucose uptake and glucose metabolism; however, it activates AMPK, shifts basal glucose metabolism towards oxidation and reduces lactate production in L6 rat skeletal muscle cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Blotting, Western
  • Cells, Cultured
  • Citrate (si)-Synthase / metabolism
  • Creatine / pharmacology*
  • Cyclic AMP-Dependent Protein Kinases / physiology*
  • Glucose / metabolism*
  • Glucose Transporter Type 4
  • Glycogen / biosynthesis
  • Glycogen / metabolism
  • Lactic Acid / metabolism*
  • Monosaccharide Transport Proteins / metabolism
  • Muscle Fibers, Skeletal / drug effects
  • Muscle Fibers, Skeletal / metabolism
  • Muscle Proteins*
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism*
  • Oxidation-Reduction
  • Phosphocreatine / metabolism
  • Phosphorylation
  • Proto-Oncogene Proteins c-myc / metabolism
  • Rats


  • Glucose Transporter Type 4
  • Monosaccharide Transport Proteins
  • Muscle Proteins
  • Proto-Oncogene Proteins c-myc
  • Slc2a4 protein, rat
  • Phosphocreatine
  • Lactic Acid
  • Adenosine Triphosphate
  • Glycogen
  • Citrate (si)-Synthase
  • Cyclic AMP-Dependent Protein Kinases
  • Glucose
  • Creatine