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Topics {✒️}

peroxisome proliferator-activated receptor-δ peroxisome proliferator-activated receptors pparβ/δ-deficient mice peroxisome proliferator-activated receptor amp-activated protein kinase tunicamycin-induced er stress protects leptin-deficient mice manuel vázquez-carrera hypoxia-regulated glucose transport month download article/chapter extracellular-signal-regulated kinase pparβ/δ activation lipid-induced insulin resistance endoplasmic reticulum stress endoplasmic-reticulum stress acute-phase reactants pparalpha-leukotriene b4 pathway ampk-pparα-dependent pathway anna maria gómez-foix pparβ/δ upregulates pparδ-dependent pathways nuclear receptor superfamily pcdna3/pampkalpha2-k45r plasmid nuclear factor-kappab increased cd36 protein oxygen-regulated protein 150 article diabetologia aims full article pdf stop-niddm study group high-fat diet liliane michalik ppar delta unsaturated fatty acids xavier palomer amp kinase privacy choices/manage cookies related subjects language advisory service protein kinase author information authors proteasome-dependent activation ampk-dependent mechanism ciber de diabetes κb ire1α article salvadó 2-deoxy-glucose acc2 impaired glucose tolerance fiber-type switching emma barroso check access

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         headline:PPARβ/δ prevents endoplasmic reticulum stress-associated inflammation and insulin resistance in skeletal muscle cells through an AMPK-dependent mechanism
         description:Endoplasmic reticulum (ER) stress, which is involved in the link between inflammation and insulin resistance, contributes to the development of type 2 diabetes mellitus. In this study, we assessed whether peroxisome proliferator-activated receptor (PPAR)β/δ prevented ER stress-associated inflammation and insulin resistance in skeletal muscle cells. Studies were conducted in mouse C2C12 myotubes, in the human myogenic cell line LHCN-M2 and in skeletal muscle from wild-type and PPARβ/δ-deficient mice and mice exposed to a high-fat diet. The PPARβ/δ agonist GW501516 prevented lipid-induced ER stress in mouse and human myotubes and in skeletal muscle of mice fed a high-fat diet. PPARβ/δ activation also prevented thapsigargin- and tunicamycin-induced ER stress in human and murine skeletal muscle cells. In agreement with this, PPARβ/δ activation prevented ER stress-associated inflammation and insulin resistance, and glucose-intolerant PPARβ/δ-deficient mice showed increased phosphorylated levels of inositol-requiring 1 transmembrane kinase/endonuclease-1α in skeletal muscle. Our findings demonstrate that PPARβ/δ activation prevents ER stress through the activation of AMP-activated protein kinase (AMPK), and the subsequent inhibition of extracellular-signal-regulated kinase (ERK)1/2 due to the inhibitory crosstalk between AMPK and ERK1/2, since overexpression of a dominant negative AMPK construct (K45R) reversed the effects attained by PPARβ/δ activation. Overall, these findings indicate that PPARβ/δ prevents ER stress, inflammation and insulin resistance in skeletal muscle cells by activating AMPK.
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            address:
               name:Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona, Spain
               type:PostalAddress
            type:Organization
            name:Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Diseases (CIBERDEM), Spain
            address:
               name:Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Diseases (CIBERDEM), Spain
               type:PostalAddress
            type:Organization
      name:Liliane Michalik
      affiliation:
            name:University of Lausanne
            address:
               name:Center for Integrative Genomics, National Research Center Frontiers in Genetics, University of Lausanne, Lausanne, Switzerland
               type:PostalAddress
            type:Organization
      name:Walter Wahli
      affiliation:
            name:University of Lausanne
            address:
               name:Center for Integrative Genomics, National Research Center Frontiers in Genetics, University of Lausanne, Lausanne, Switzerland
               type:PostalAddress
            type:Organization
            name:Nanyang Technological University
            address:
               name:Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Republic of Singapore
               type:PostalAddress
            type:Organization
      name:Manuel Vázquez-Carrera
      affiliation:
            name:University of Barcelona
            address:
               name:Department of Pharmacology and Therapeutic Chemistry, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain
               type:PostalAddress
            type:Organization
            name:Institute of Biomedicine of the University of Barcelona (IBUB)
            address:
               name:Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona, Spain
               type:PostalAddress
            type:Organization
            name:Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Diseases (CIBERDEM), Spain
            address:
               name:Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Diseases (CIBERDEM), Spain
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Pharmacology and Therapeutic Chemistry, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain
      name:Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona, Spain
      name:Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Diseases (CIBERDEM), Spain
      name:Department of Pharmacology and Therapeutic Chemistry, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain
      name:Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona, Spain
      name:Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Diseases (CIBERDEM), Spain
      name:Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona, Spain
      name:Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Diseases (CIBERDEM), Spain
      name:Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Barcelona, Spain
      name:Department of Pharmacology and Therapeutic Chemistry, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain
      name:Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona, Spain
      name:Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Diseases (CIBERDEM), Spain
      name:Center for Integrative Genomics, National Research Center Frontiers in Genetics, University of Lausanne, Lausanne, Switzerland
      name:Center for Integrative Genomics, National Research Center Frontiers in Genetics, University of Lausanne, Lausanne, Switzerland
      name:Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Republic of Singapore
      name:Department of Pharmacology and Therapeutic Chemistry, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain
      name:Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona, Spain
      name:Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Diseases (CIBERDEM), Spain
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      cssSelector:.main-content

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