Abstract
Peroxisome proliferator-activated receptor-delta (PPARdelta) activation enhances skeletal muscle fatty acid oxidation and improves whole body glucose homeostasis and insulin sensitivity. Recently, GW501516, a selective PPARdelta agonist, was reported to increase glucose uptake in human skeletal myotubes by an AMPK-dependent mechanism that may contribute to the improved glucose tolerance. Here, we demonstrate that whilst GW501516 increases expression of PGC-1alpha and CPT-1 and stimulates fatty-acid oxidation in L6 myotubes, it fails to enhance insulin sensitivity, AMPK activity or glucose uptake and storage. Our findings exclude sarcolemmal glucose transport as a potential target for the therapeutic action of PPARdelta agonists in skeletal muscle.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Carnitine O-Palmitoyltransferase / metabolism
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Cell Line
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Fatty Acids / metabolism*
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Glucose / metabolism*
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Glycogen / biosynthesis
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Insulin / pharmacology*
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Muscle Fibers, Skeletal / drug effects
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Muscle Fibers, Skeletal / metabolism
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Muscle, Skeletal / drug effects*
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Muscle, Skeletal / metabolism
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Oxidation-Reduction / drug effects
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PPAR delta / agonists*
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PPAR delta / metabolism*
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
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RNA-Binding Proteins / metabolism
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Rats
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Sensitivity and Specificity
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Thiazoles / pharmacology*
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Transcription Factors / metabolism
Substances
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Fatty Acids
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GW 501516
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Insulin
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PPAR delta
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
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Ppargc1a protein, rat
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RNA-Binding Proteins
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Thiazoles
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Transcription Factors
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Glycogen
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Carnitine O-Palmitoyltransferase
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Glucose