Sphingolipids: agents provocateurs in the pathogenesis of insulin resistance

C. Lipina, H. S. Hundal (Lead / Corresponding author)

    Research output: Contribution to journalReview article

    52 Citations (Scopus)

    Abstract

    Obesity is a major risk factor for a variety of chronic diseases, including diabetes mellitus, and comorbidities such as cardiovascular disorders. Despite recommended alterations in lifestyle, including physical activity and energy restriction, being the foundation of any anti-obesity therapy, this approach has so far proved to be of little success in tackling this major public health concern. Because of this, alternative means of tackling this problem are currently being investigated, including pharmacotherapeutic intervention. Consequently, much attention has been directed towards elucidating the molecular mechanisms underlying the development of insulin resistance. This review discusses some of these potential mechanisms, with particular focus on the involvement of the sphingolipid ceramide. Various factors associated with obesity, such as saturated fatty acids and inflammatory cytokines, promote the synthesis of ceramide and other intermediates. Furthermore, studies performed in cultured cells and in vivo associate these sphingolipids with impaired insulin action. In light of this, we provide an account of the research investigating how pharmacological inhibition or genetic manipulation of enzymes involved in regulating sphingolipid synthesis can attenuate the insulin-desensitising effects of these obesity-related factors. By doing so, we outline potential therapeutic targets that may prove useful in the treatment of metabolic disorders.

    Original languageEnglish
    Pages (from-to)1596-1607
    Number of pages12
    JournalDiabetologia
    Volume54
    Issue number7
    DOIs
    Publication statusPublished - Jul 2011

    Keywords

    • Adipose tissue
    • Caveolae
    • Ceramide
    • Gangliosides
    • GM3
    • Skeletal muscle
    • Sphingomyelin
    • PKB/Akt
    • PROTEIN-KINASE-C
    • SKELETAL-MUSCLE CELLS
    • PLECKSTRIN HOMOLOGY DOMAIN
    • SATURATED FATTY-ACIDS
    • GANGLIOSIDE GM3
    • CERAMIDE SYNTHESIS
    • INDUCED APOPTOSIS
    • GLUCOSE-UPTAKE
    • IN-VIVO
    • DE-NOVO

    Research Output

    • 52 Citations
    • 1 Article

    Erratum to: Sphingolipids: agents provocateurs in the pathogenesis of insulin resistance

    Lipina, C. & Hundal, H. S., Nov 2011, In : Diabetologia. 54, 11, p. 2969 1 p.

    Research output: Contribution to journalArticle

    Cite this