The PPARdelta agonist, GW501516, promotes fatty acid oxidation but has no direct effect on glucose utilisation or insulin sensitivity in rat L6 skeletal muscle cells

Nikolaos Dimopoulos, Maria Watson, Charlotte Green, Harinder S Hundal

    Research output: Contribution to journalArticlepeer-review

    29 Citations (Scopus)

    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.
    Original languageEnglish
    Pages (from-to)4743-4748
    Number of pages6
    JournalFEBS Letters
    Volume581
    Issue number24
    DOIs
    Publication statusPublished - 2007

    Keywords

    • Animals
    • Carnitine O-Palmitoyltransferase
    • Cell Line
    • Fatty Acids
    • Glucose
    • Glycogen
    • Insulin
    • Muscle Fibers, Skeletal
    • Muscle, Skeletal
    • Oxidation-Reduction
    • PPAR delta
    • RNA-Binding Proteins
    • Rats
    • Sensitivity and Specificity
    • Thiazoles
    • Transcription Factors

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