Chapter

Sphingolipids and Metabolic Disease

Volume 721 of the series Advances in Experimental Medicine and Biology pp 99-119

Glycosphingolipids and Insulin Resistance

  • Johannes M. AertsAffiliated withDepartment of Medical Biochemistry, University of Amsterdam
  • , Rolf G. BootAffiliated withDepartment of Medical Biochemistry, University of Amsterdam
  • , Marco van EijkAffiliated withDepartment of Medical Biochemistry, University of Amsterdam
  • , Johanna GroenerAffiliated withDepartment of Medical Biochemistry, University of Amsterdam
  • , Nora BijlAffiliated withDepartment of Medical Biochemistry, University of Amsterdam
  • , Elisa LombardoAffiliated withDepartment of Medical Biochemistry, University of Amsterdam
  • , Florence M. BietrixAffiliated withDepartment of Medical Biochemistry, University of Amsterdam
  • , Nick DekkerAffiliated withDepartment of Medical Biochemistry, University of Amsterdam
  • , Albert K. GroenAffiliated withDepartment of Medical Biochemistry, University of Amsterdam
    • , Roelof OttenhoffAffiliated withDepartment of Medical Biochemistry, University of Amsterdam
    • , Cindy van RoomenAffiliated withDepartment of Medical Biochemistry, University of Amsterdam
    • , Jan AtenAffiliated withDepartment of Pathology, University of Amsterdam
    • , Mireille SerlieAffiliated withDepartment of Internal Medicine, Academic Medical Center, University of Amsterdam
    • , Mirjam LangeveldAffiliated withDepartment of Internal Medicine, Academic Medical Center, University of Amsterdam
    • , Tom WennekesAffiliated withLeiden Institute of Chemistry, Department of Bioorganic Synthesis, Gorlaeus Laboratories, Leiden University
    • , Hermen S. OverkleeftAffiliated withLeiden Institute of Chemistry, Department of Bioorganic Synthesis, Gorlaeus Laboratories, Leiden University

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Abstract

Glycosphingolipids are structural membrane components, residing largely in the plasma membrane with their sugar-moieties exposed at the cell’s surface. In recent times a crucial role for glycosphingolipids in insulin resistance has been proposed. A chronic state of insulin resistance is a rapidly increasing disease condition in Western and developing countries. It is considered to be the major underlying cause of the metabolic syndrome, a combination of metabolic abnormalities that increases the risk for an individual to develop Type 2 diabetes, obesity, cardiovascular disease, polycystic ovary syndrome and nonalcoholic fatty liver disease. As discussed in this chapter, the evidence for a direct regulatory interaction of glycosphingolipids with insulin signaling is still largely indirect. However, the recent finding in animal models that pharmacological reduction of glycosphingolipid biosynthesis ameliorates insulin resistance and prevents some manifestations of metabolic syndrome, supports the view that somehow glycosphingolipids act as critical regulators, Importantly, since reductions in glycosphingolipid biosynthesis have been found to be well tolerated, such approaches may have a therapeutic potential.