Translocation of myocardial GLUT-4 and increased glucose uptake through activation of AMPK by AICAR

Am J Physiol. 1999 Aug;277(2):H643-9. doi: 10.1152/ajpheart.1999.277.2.H643.


Insulin increases glucose uptake through the translocation of GLUT-4 via a pathway mediated by phosphatidylinositol 3-kinase (PI3K). In contrast, myocardial glucose uptake during ischemia and hypoxia is stimulated by the translocation of GLUT-4 to the surface of cardiac myocytes through a PI3K-independent pathway that has not been characterized. AMP-activated protein kinase (AMPK) activity is also increased by myocardial ischemia, and we examined whether AMPK stimulates glucose uptake and GLUT-4 translocation. In isolated rat ventricular papillary muscles, 5-aminoimidazole-4-carboxyamide-1-beta-D-ribofuranoside (AICAR), an activator of AMPK, as well as cyanide-induced chemical hypoxia and insulin, increased 2-[(3)H]deoxyglucose uptake two- to threefold. Wortmannin, a PI3K inhibitor, did not affect either the AICAR- or the cyanide-stimulated increase in deoxyglucose uptake but eliminated the insulin-stimulated increase in deoxyglucose uptake. Immunofluorescence studies demonstrated translocation of GLUT-4 to the myocyte sarcolemma in response to stimulation with AICAR, cyanide, or insulin. Preincubation of papillary muscles with the kinase inhibitor iodotubercidin or adenine 9-beta-D-arabinofuranoside (araA), a precursor of araATP (a competitive inhibitor of AMPK), decreased AICAR- and cyanide-stimulated glucose uptake but did not affect basal or insulin-stimulated glucose uptake. In vivo infusion of AICAR caused myocardial AMPK activation and GLUT-4 translocation in the rat. We conclude that AMPK activation increases cardiac muscle glucose uptake through translocation of GLUT-4 via a pathway that is independent of PI3K. These findings suggest that AMPK activation may be important in ischemia-induced translocation of GLUT-4 in the heart.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AMP-Activated Protein Kinases
  • Aminoimidazole Carboxamide / analogs & derivatives*
  • Aminoimidazole Carboxamide / pharmacology
  • Animals
  • Biological Transport
  • Enzyme Activation
  • Glucose / metabolism*
  • Glucose Transporter Type 4
  • In Vitro Techniques
  • Male
  • Monosaccharide Transport Proteins / metabolism*
  • Multienzyme Complexes / metabolism*
  • Muscle Proteins*
  • Myocardium / cytology
  • Myocardium / metabolism*
  • Protein-Serine-Threonine Kinases / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Ribonucleotides / pharmacology*
  • Sarcolemma / metabolism


  • Glucose Transporter Type 4
  • Monosaccharide Transport Proteins
  • Multienzyme Complexes
  • Muscle Proteins
  • Ribonucleotides
  • Slc2a4 protein, rat
  • Aminoimidazole Carboxamide
  • Protein-Serine-Threonine Kinases
  • AMP-Activated Protein Kinases
  • AICA ribonucleotide
  • Glucose