title: Regulation of glucose transporter expression in cardiac myocytes: p38 MAPK is a strong inducer of GLUT4.
abstract: OBJECTIVE
  In vivo differentiation of cardiac myocytes is associated with downregulation of the glucose transporter isoform GLUT1 and upregulation of the isoform GLUT4. Adult rat cardiomyocytes in primary culture undergo spontaneous dedifferentiation, followed by spreading and partial redifferentiation, which can be influenced by growth factors. We used this model to study the signaling mechanisms modifying the expression of GLUT4 in cardiac myocytes.
  
  
  RESULTS
  Adult rat cardiomyocytes in primary culture exhibited spontaneous upregulation of GLUT1 and downregulation of GLUT4, suggesting resumption of a fetal program of GLUT gene expression. Treatment with IGF-1 and, to a minor extent, FGF-2 resulted in restored expression of GLUT4 protein and mRNA. Activation of p38 MAPK mediated the increased expression of GLUT4 in response to IGF-1. Transient transfection experiments in neonatal cardiac myocytes confirmed that p38 MAPK could activate the glut4 promoter. Electrophoretic mobility shift assay in adult rat cardiomyocytes and transient transfection experiments in neonatal cardiac myocytes indicated that MEF2 was the main transcription factor transducing the effect of p38 MAPK activation on the glut4 promoter.
  
  
  CONCLUSIONS
  Spontaneous dedifferentiation of adult rat cardiomyocytes in vitro is associated with downregulation of GLUT4, which can be reversed by treatment with IGF-1. The effect of IGF-1 is mediated by the p38 MAPK/MEF2 axis, which is a strong inducer of GLUT4 expression.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Geneva University Hospitals, Rue Micheli-Du-Crest 24, 1211 Geneva 14, Switzerland. christophe.montessuit@hcuge.ch
authors.forename: Christophe
authors.initials: C
authors.lastname: Montessuit
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rosenblatt-Velin
authors.forename: Irène
authors.initials: I
authors.lastname: Papageorgiou
authors.forename: Lis
authors.initials: L
authors.lastname: Campos
authors.forename: Corinne
authors.initials: C
authors.lastname: Pellieux
authors.forename: Tatiana
authors.initials: T
authors.lastname: Palma
authors.forename: René
authors.initials: R
authors.lastname: Lerch
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D024202:Electrophoretic Mobility Shift Assay; D004789:Enzyme Activation; D016222:Fibroblast Growth Factor 2 / Q000032:analysis / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005818:Genetic Engineering; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D015151:Immunoblotting / Q000379:methods; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000378:metabolism; D008156:Luciferases / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495679:Slc2a1 protein, rat; C495694:Slc2a4 protein, rat; D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I; D008156:Luciferases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases