Fuel selection in human skeletal muscle in insulin resistance: A reexamination

David E. Kelley, Lawrence J. Mandarino

    Research output: Contribution to journalReview article

    668 Scopus citations

    Abstract

    For many years, the Randle glucose fatty acid cycle has been invoked to explain insulin resistance in skeletal muscle of patients with type 2 diabetes or obesity. Increased fat oxidation was hypothesized to reduce glucose metabolism. The results of a number of investigations have shown that artificially increasing fat oxidation by provision of excess lipid does decrease glucose oxidation in the whole body. However, results obtained with rodent or human systems that more directly examined muscle fuel selection have found that skeletal muscle in insulin resistance is accompanied by increased, rather than decreased, muscle glucose oxidation under basal conditions and decreased glucose oxidation under insulin-stimulated circumstances, producing a state of 'metabolic inflexibility.' Such a situation could contribute to the accumulation of triglyceride within the myocyte, as has been observed in insulin resistance. Recent knowledge of insulin receptor signaling indicates that the accumulation of lipid products in muscle can interfere with insulin signaling and produce insulin resistance. Therefore, although the Randle cycle is a valid physiological principle, it may not explain insulin resistance in skeletal muscle.

    Original languageEnglish (US)
    Pages (from-to)677-683
    Number of pages7
    JournalDiabetes
    Volume49
    Issue number5
    DOIs
    StatePublished - May 2000

    ASJC Scopus subject areas

    • Internal Medicine
    • Endocrinology, Diabetes and Metabolism

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