The role of sphingolipid signalling in diabetes-associated pathologies (Review)

Mei Ng, Carol Wadham, Olga Sukocheva

    Research output: Contribution to journalArticlepeer-review

    31 Citations (Scopus)

    Abstract

    Sphingosine kinase (SphK) is an important signalling enzyme that catalyses the phosphorylation of sphingosine (Sph) to form sphingosine-1-phosphate (S1P). The multifunctional lipid, S1P binds to a family of five G protein-coupled receptors (GPCRs). As an intracellular second messenger, S1P activates key signalling cascades responsible for the maintenance of sphingolipid metabolism, and has been implicated in the progression of cancer, and the development of other inflammatory and metabolic diseases. SphK and S1P are critical molecules involved in the regulation of various cellular metabolic processes, such as cell proliferation, survival, apoptosis, adhesion and migration. There is strong evidence supporting the critical roles of SphK and S1P in the progression of diabetes mellitus, including insulin sensitivity and insulin secretion, pancreatic ß-cell apoptosis, and the development of diabetic inflammatory state. In this review, we summarise the current state of knowledge for SphK/S1P signalling effects, associated with the development of insulin resistance, pancreatic ß-cell death and the vascular complications of diabetes mellitus.

    Original languageEnglish
    Pages (from-to)243-252
    Number of pages10
    JournalINTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
    Volume39
    Issue number2
    DOIs
    Publication statusPublished - 2017

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