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Molecular and Cellular Biochemistry

, Volume 299, Issue 1–2, pp 5–18 | Cite as

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

  • Susan L. M. Coort
  • Arend Bonen
  • Ger J. van der Vusse
  • Jan F. C. Glatz
  • Joost J. F. P. LuikenEmail author
Article

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.

Keywords

CD36 fatty acid uptake GLUT4 type-2 diabetes 

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Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  • Susan L. M. Coort
    • 1
  • Arend Bonen
    • 2
  • Ger J. van der Vusse
    • 3
  • Jan F. C. Glatz
    • 1
  • Joost J. F. P. Luiken
    • 1
    • 4
    • 5
    Email author
  1. 1.Department of Molecular Genetics, Cardiovascular Research Institute Maastricht (CARIM)Maastricht UniversityMaastrichtThe Netherlands
  2. 2.Department of Human Biology and Nutritional SciencesGuelph UniversityGuelphCanada
  3. 3.Department of Physiology, Cardiovascular Research Institute Maastricht (CARIM)Maastricht UniversityMaastrichtThe Netherlands
  4. 4.Department of Biochemical Physiology and Institute of BiomembranesUtrecht UniversityUtrechtThe Netherlands
  5. 5.Department of Molecular Genetics, CARIMMaastricht UniversityMaastrichtThe Netherlands

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