Effects of AICAR and exercise on insulin-stimulated glucose uptake, signaling, and GLUT-4 content in rat muscles

J Appl Physiol (1985). 2003 Apr;94(4):1373-9. doi: 10.1152/japplphysiol.00250.2002. Epub 2002 Dec 20.


Physical activity is known to increase insulin action in skeletal muscle, and data have indicated that 5'-AMP-activated protein kinase (AMPK) is involved in the molecular mechanisms behind this beneficial effect. 5-Aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) can be used as a pharmacological tool to repetitively activate AMPK, and the objective of this study was to explore whether the increase in insulin-stimulated glucose uptake after either long-term exercise or chronic AICAR administration was followed by fiber-type-specific changes in insulin signaling and/or changes in GLUT-4 expression. Wistar rats were allocated into three groups: an exercise group trained on treadmill for 5 days, an AICAR group exposed to daily subcutaneous injections of AICAR, and a sedentary control group. AMPK activity, insulin-stimulated glucose transport, insulin signaling, and GLUT-4 expression were determined in muscles characterized by different fiber type compositions. Both exercised and AICAR-injected animals displayed a fiber-type-specific increase in glucose transport with the most marked increase in muscles with a high content of type IIb fibers. This increase was accompanied by a concomitant increase in GLUT-4 expression. Insulin signaling as assessed by phosphatidylinositol 3-kinase and PKB/Akt activity was enhanced only after AICAR administration and in a non-fiber-type-specific manner. In conclusion, chronic AICAR administration and long-term exercise both improve insulin-stimulated glucose transport in skeletal muscle in a fiber-type-specific way, and this is associated with an increase in GLUT-4 content.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases
  • Aminoimidazole Carboxamide / analogs & derivatives*
  • Aminoimidazole Carboxamide / pharmacology*
  • Animals
  • Biological Transport
  • Glucose / pharmacokinetics*
  • Glucose Transporter Type 4
  • Guanosine / analogs & derivatives*
  • Guanosine / pharmacokinetics
  • Hypoglycemic Agents / pharmacology*
  • Immunoblotting
  • Insulin / pharmacology*
  • Insulin Receptor Substrate Proteins
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Monosaccharide Transport Proteins / metabolism*
  • Motor Activity / physiology*
  • Multienzyme Complexes / metabolism
  • Muscle Proteins*
  • Muscle, Skeletal / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Protein Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt
  • Rats
  • Rats, Wistar
  • Ribonucleotides / pharmacology*
  • Signal Transduction / drug effects*


  • Glucose Transporter Type 4
  • Hypoglycemic Agents
  • Insulin
  • Insulin Receptor Substrate Proteins
  • Intracellular Signaling Peptides and Proteins
  • Irs1 protein, rat
  • Irs2 protein, rat
  • Monosaccharide Transport Proteins
  • Multienzyme Complexes
  • Muscle Proteins
  • Phosphoproteins
  • Proto-Oncogene Proteins
  • Ribonucleotides
  • Slc2a4 protein, rat
  • 3'-O-methylguanosine
  • Guanosine
  • Aminoimidazole Carboxamide
  • Akt1 protein, rat
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • AMP-Activated Protein Kinases
  • AICA ribonucleotide
  • Glucose