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Alpha-lipoic acid increases insulin sensitivity by activating AMPK in skeletal muscle.

Abstract

Triglyceride accumulation in skeletal muscle contributes to insulin resistance in obesity. We recently showed that alpha-lipoic acid (ALA) reduces body weight and prevents the development of diabetes in diabetes-prone obese rats by reducing triglyceride accumulation in non-adipose tissues. AMP-activated protein kinase (AMPK) is a major regulator of cellular energy metabolism. We examined whether ALA lowers triglyceride accumulation in skeletal muscle by activating AMPK. Alpha2-AMPK activity was decreased in obese rats compared to control rats. Administration of ALA to obese rats increased insulin-stimulated glucose disposal in whole body and in skeletal muscle. ALA also increased fatty acid oxidation and activated AMPK in skeletal muscle. Adenovirus-mediated administration of dominant negative AMPK into skeletal muscle prevented the ALA-induced increases in fatty acid oxidation and insulin-stimulated glucose uptake. These results suggest that ALA-induced improvement of insulin sensitivity is mediated by activation of AMPK and reduced triglyceride accumulation in skeletal muscle.

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  • Authors

    , , , , , , , , ,

    Source

    MeSH

    AMP-Activated Protein Kinases
    Animals
    Diabetes Mellitus, Type 2
    Enzyme Activation
    Fatty Acids
    Glucose
    Insulin Resistance
    Lactic Acid
    Male
    Multienzyme Complexes
    Muscle, Skeletal
    Oxidation-Reduction
    Protein-Serine-Threonine Kinases
    Rats
    Rats, Inbred OLETF
    Thioctic Acid
    Triglycerides

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    15913551