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Short-term activation of peroxysome proliferator-activated receptor β/δ increases fatty acid oxidation but does not restore insulin action in muscle cells from type 2 diabetic patients

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Abstract

Defective fatty acid oxidation in skeletal muscle is one of the possible causes of insulin resistance. Peroxisome proliferator-activated receptor β activators are strong inducers of fatty acid oxidation. The aim of this study was to verify whether activation of fatty acid oxidation by PPARβ agonists in human skeletal muscle cells prepared from type 2 diabetic patients could improve the reduced responses to insulin that characterized this cell model. GW0742 (10 nM) significantly increased fatty acid oxidation and oxidative gene expression in myotubes prepared from both healthy subjects and type 2 diabetic patients. In cells from control subjects, incubation with the agonist for 48 h affected neither insulin-induced rate of glycogen synthesis nor the phosphorylation state of protein kinase B (PKB serine 473). Myotubes from type 2 diabetic patients displayed marked reduction in the effects of insulin on glycogen synthesis and on PKB phosphorylation. However, treatment with PPARβ agonists did not restore these defects. Therefore, these results indicate that induction of fatty acid oxidation with PPARβ activators during short-term exposition is not sufficient to correct for insulin resistance in muscle cells from type 2 diabetic patients. This suggests that additional studies are needed to better characterize the link between fatty acid oxidation and insulin sensitivity in humans.

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Acknowledgements

The authors would like to thank J. Peyrat, C. Urbain, and V. Berbe for excellent technical assistance. We also would like to thank Dr. D. Pruneau for helpful discussions and Merck Research Laboratories and GlaxoSmithKline for providing of PPARβ agonists. This work was supported in part by research grants from INSERM (PNRD 2004) and from Fournier Pharma (Daix, France). D. Cozzone and C. Debard are recipients of a doctoral fellowship from the Ministère de l’Enseignement Superieur et de la Recherche.

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Authors and Affiliations

  1. INSERM U-449, INRA U-1235, R. Laennec Faculty of Medicine, Human Nutrition Research Center, Claude Bernard-Lyon 1 University, Rue G. Paradin, 69372, Lyon, Cedex 08, France

    Cyrille Debard, Delphine Cozzone, Nadège Ricard, Julien Vouillarmet, Emmanuel Disse, Martine Laville & Hubert Vidal

  2. Department of Endocrinology, Diabetology and Nutrition, E. Herriot Hospital, Lyon, France

    Emmanuel Disse, Martine Laville & Hubert Vidal

  3. Department of Pharmacology, Fournier Pharma, Daix, France

    Bernadette Husson

Authors
  1. Cyrille Debard
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  2. Delphine Cozzone
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  3. Nadège Ricard
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  4. Julien Vouillarmet
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  5. Emmanuel Disse
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  6. Bernadette Husson
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  7. Martine Laville
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  8. Hubert Vidal
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Corresponding author

Correspondence to Hubert Vidal.

Additional information

C. Debard and D. Cozzone contributed equally to this work.

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Debard, C., Cozzone, D., Ricard, N. et al. Short-term activation of peroxysome proliferator-activated receptor β/δ increases fatty acid oxidation but does not restore insulin action in muscle cells from type 2 diabetic patients. J Mol Med 84, 747–752 (2006). https://doi.org/10.1007/s00109-006-0077-x

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  • DOI: https://doi.org/10.1007/s00109-006-0077-x

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