title: (13)C metabolic flux analysis shows that resistin impairs the metabolic response to insulin in L6E9 myotubes.
abstract: BACKGROUND
  It has been suggested that the adipokine resistin links obesity and insulin resistance, although how resistin acts on muscle metabolism is controversial. We aimed to quantitatively analyse the effects of resistin on the glucose metabolic flux profile and on insulin response in L6E9 myotubes at the metabolic level using a tracer-based metabolomic approach and our in-house developed software, Isodyn.
  
  
  RESULTS
  Resistin significantly increased glucose uptake and glycolysis, altering pyruvate utilisation by the cell. In the presence of resistin, insulin only slightly increased glucose uptake and glycolysis, and did not alter the flux profile around pyruvate induced by resistin. Resistin prevented the increase in gene expression in pyruvate dehydrogenase-E1 and the sharp decrease in gene expression in cytosolic phosphoenolpyruvate carboxykinase-1 induced by insulin.
  
  
  CONCLUSIONS
  These data suggest that resistin impairs the metabolic activation of insulin. This impairment cannot be explained by the activity of a single enzyme, but instead due to reorganisation of the whole metabolic flux distribution.
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, Universitat de Barcelona, Av Diagonal 643, 08028, Barcelona, Spain. shirleyguzman1@gmail.com.|Institute of Biomedicine of Universitat de Barcelona (IBUB) and CSIC-Associated Unit, Barcelona, Spain. shirleyguzman1@gmail.com.
authors.forename: Shirley
authors.initials: S
authors.lastname: Guzmán
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, Universitat de Barcelona, Av Diagonal 643, 08028, Barcelona, Spain. silviamarin@ub.edu.|Institute of Biomedicine of Universitat de Barcelona (IBUB) and CSIC-Associated Unit, Barcelona, Spain. silviamarin@ub.edu.
authors.forename: Silvia
authors.initials: S
authors.lastname: Marin
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, Universitat de Barcelona, Av Diagonal 643, 08028, Barcelona, Spain. amiranda@ub.edu.|Institute of Biomedicine of Universitat de Barcelona (IBUB) and CSIC-Associated Unit, Barcelona, Spain. amiranda@ub.edu.
authors.forename: Anibal
authors.initials: A
authors.lastname: Miranda
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, Universitat de Barcelona, Av Diagonal 643, 08028, Barcelona, Spain. selivanov@ub.edu.|Institute of Biomedicine of Universitat de Barcelona (IBUB) and CSIC-Associated Unit, Barcelona, Spain. selivanov@ub.edu.
authors.forename: Vitaly A
authors.initials: VA
authors.lastname: Selivanov
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, Universitat de Barcelona, Av Diagonal 643, 08028, Barcelona, Spain. josepcentelles@ub.edu.|Institute of Biomedicine of Universitat de Barcelona (IBUB) and CSIC-Associated Unit, Barcelona, Spain. josepcentelles@ub.edu.
authors.forename: Josep J
authors.initials: JJ
authors.lastname: Centelles
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), UMR 1048, Toulouse, France. Romain.Harmancey@wanadoo.fr.|Université Toulouse III Paul-Sabatier, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Equipe n°7, Toulouse, France. Romain.Harmancey@wanadoo.fr.
authors.forename: Romain
authors.initials: R
authors.lastname: Harmancey
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), UMR 1048, Toulouse, France. Fatima.smith-rouet@inserm.fr.|Université Toulouse III Paul-Sabatier, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Equipe n°7, Toulouse, France. Fatima.smith-rouet@inserm.fr.
authors.forename: Fatima
authors.initials: F
authors.lastname: Smih
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), UMR 1048, Toulouse, France. aniturkieh@hotmail.com.|Université Toulouse III Paul-Sabatier, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Equipe n°7, Toulouse, France. aniturkieh@hotmail.com.
authors.forename: Annie
authors.initials: A
authors.lastname: Turkieh
authors.affiliation: Animal Cell Technology Group, Biotechnology Research Institute, National Research Council Canada, Montreal, QC, Canada. yves.durocher@cnrc-nrc.gc.ca.
authors.forename: Yves
authors.initials: Y
authors.lastname: Durocher
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, Universitat de Barcelona, Av Diagonal 643, 08028, Barcelona, Spain. antonio.zorzano@irbbarcelona.org.|Institute for Research in Biomedicine (IRB Barcelona) and CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain. antonio.zorzano@irbbarcelona.org.
authors.forename: Antonio
authors.initials: A
authors.lastname: Zorzano
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), UMR 1048, Toulouse, France. philippe.rouet@inserm.fr.|Université Toulouse III Paul-Sabatier, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Equipe n°7, Toulouse, France. philippe.rouet@inserm.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Rouet
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, Universitat de Barcelona, Av Diagonal 643, 08028, Barcelona, Spain. martacascante@ub.edu.|Institute of Biomedicine of Universitat de Barcelona (IBUB) and CSIC-Associated Unit, Barcelona, Spain. martacascante@ub.edu.
authors.forename: Marta
authors.initials: M
authors.lastname: Cascante
mesh_terms: D000818:Animals; D002247:Carbon Isotopes / Q000378:metabolism*; D019295:Computational Biology; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D064688:Metabolic Flux Analysis / Q000379:methods*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000378:metabolism; D030481:Pyruvate Dehydrogenase (Lipoamide) / Q000378:metabolism; D051381:Rats; D052243:Resistin / Q000378:metabolism*; D012984:Software
chemical_list: D002247:Carbon Isotopes; D007328:Insulin; D052243:Resistin; D030481:Pyruvate Dehydrogenase (Lipoamide); D019764:Phosphoenolpyruvate Carboxykinase (ATP); D005947:Glucose