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Cardiac substrate uptake and metabolism in obesity and type-2 diabetes: Role of sarcolemmal substrate transporters

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Abstract

Cardiovascular disease is the primary cause of death in obesity and type-2 diabetes mellitus (T2DM). Alterations in substrate metabolism are believed to be involved in the development of both cardiac dysfunction and insulin resistance in these conditions. Under physiological circumstances the heart utilizes predominantly long-chain fatty acids (LCFAs) (60–70%), with the remainder covered by carbohydrates, i.e., glucose (20%) and lactate (10%). The cellular uptake of both LCFA and glucose is regulated by the sarcolemmal amount of specific transport proteins, i.e., fatty acid translocase (FAT)/CD36 and GLUT4, respectively. These transport proteins are not only present at the sarcolemma, but also in intracellular storage compartments. Both an increased workload and the hormone insulin induce translocation of FAT/CD36 and GLUT4 to the sarcolemma. In this review, recent findings on the insulin and contraction signalling pathways involved in substrate uptake and utilization by cardiac myocytes under physiological conditions are discussed. New insights in alterations in substrate uptake and utilization during insulin resistance and its progression towards T2DM suggest a pivotal role for substrate transporters. During the development of obesity towards T2DM alterations in cardiac lipid homeostasis were found to precede alterations in glucose homeostasis. In the early stages of T2DM, relocation of FAT/CD36 to the sarcolemma is associated with the myocardial accumulation of triacylglycerols (TAGs) eventually leading to an impaired insulin-stimulated GLUT4-translocation. These novel insights may result in new strategies for the prevention of development of cardiac dysfunction and insulin resistance in obesity and T2DM.

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Authors and Affiliations

  1. Department of Molecular Genetics, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands

    Susan L. M. Coort, Jan F. C. Glatz & Joost J. F. P. Luiken

  2. Department of Human Biology and Nutritional Sciences, Guelph University, Guelph, Ontario, Canada

    Arend Bonen

  3. Department of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands

    Ger J. van der Vusse

  4. Department of Biochemical Physiology and Institute of Biomembranes, Utrecht University, Utrecht, The Netherlands

    Joost J. F. P. Luiken

  5. Department of Molecular Genetics, CARIM, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands

    Joost J. F. P. Luiken

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  1. Susan L. M. Coort
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Correspondence to Joost J. F. P. Luiken.

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Coort, S.L.M., Bonen, A., van der Vusse, G.J. et al. Cardiac substrate uptake and metabolism in obesity and type-2 diabetes: Role of sarcolemmal substrate transporters. Mol Cell Biochem 299, 5–18 (2007). https://doi.org/10.1007/s11010-005-9030-5

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