title: Short-term activation of peroxysome proliferator-activated receptor beta/delta increases fatty acid oxidation but does not restore insulin action in muscle cells from type 2 diabetic patients.
abstract: Defective fatty acid oxidation in skeletal muscle is one of the possible causes of insulin resistance. Peroxisome proliferator-activated receptor beta activators are strong inducers of fatty acid oxidation. The aim of this study was to verify whether activation of fatty acid oxidation by PPARbeta 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 PPARbeta agonists did not restore these defects. Therefore, these results indicate that induction of fatty acid oxidation with PPARbeta 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.
authors.affiliation: 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.
authors.forename: Cyrille
authors.initials: C
authors.lastname: Debard
authors.forename: Delphine
authors.initials: D
authors.lastname: Cozzone
authors.forename: Nadège
authors.initials: N
authors.lastname: Ricard
authors.forename: Julien
authors.initials: J
authors.lastname: Vouillarmet
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Disse
authors.forename: Bernadette
authors.initials: B
authors.lastname: Husson
authors.forename: Martine
authors.initials: M
authors.lastname: Laville
authors.forename: Hubert
authors.initials: H
authors.lastname: Vidal
mesh_terms: D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology*; D005260:Female; D006003:Glycogen / Q000096:biosynthesis; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D010084:Oxidation-Reduction / Q000187:drug effects; D047494:PPAR delta / Q000378:metabolism*; D048068:PPAR-beta / Q000819:agonists / Q000378:metabolism*; D019308:Palmitic Acid / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors; D010636:Phenols; D013438:Sulfhydryl Compounds
chemical_list: D006003:Glycogen; D007328:Insulin; D047494:PPAR delta; D048068:PPAR-beta; D019308:Palmitic Acid; D051057:Proto-Oncogene Proteins c-akt; D013844:Thiazoles; C479979:(4-(((2-(3-fluoro-4-(trifluoromethyl)phenyl)-4-methyl-1,3-thiazol-5-yl)methyl)sulfanyl)-2-methylphenoxy)acetic acid; D010636:Phenols; D013438:Sulfhydryl Compounds