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    Glucagon-like peptide-1 (GLP-1) and the regulation of human invariant natural killer T cells: lessons from obesity, diabetes and psoriasis.

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    Authors
    Hogan, A E
    Tobin, A M
    Ahern, T
    Corrigan, M A
    Gaoatswe, G
    Jackson, R
    O'Reilly, V
    Lynch, L
    Doherty, D G
    Moynagh, P N
    Kirby, B
    O'Connell, J
    O'Shea, D
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    Affiliation
    Department of Endocrinology, St Vincent's University Hospital, University College Dublin, Dublin 4, Ireland.
    Issue Date
    2011-11
    
    Metadata
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    Citation
    Glucagon-like peptide-1 (GLP-1) and the regulation of human invariant natural killer T cells: lessons from obesity, diabetes and psoriasis. 2011, 54 (11):2745-54 Diabetologia
    Journal
    Diabetologia
    URI
    http://hdl.handle.net/10147/146583
    DOI
    10.1007/s00125-011-2232-3
    PubMed ID
    21744074
    Abstract
    The innate immune cells, invariant natural killer T cells (iNKT cells), are implicated in the pathogenesis of psoriasis, an inflammatory condition associated with obesity and other metabolic diseases, such as diabetes and dyslipidaemia. We observed an improvement in psoriasis severity in a patient within days of starting treatment with an incretin-mimetic, glucagon-like peptide-1 (GLP-1) receptor agonist. This was independent of change in glycaemic control. We proposed that this unexpected clinical outcome resulted from a direct effect of GLP-1 on iNKT cells.
    We measured circulating and psoriatic plaque iNKT cell numbers in two patients with type 2 diabetes and psoriasis before and after commencing GLP-1 analogue therapy. In addition, we investigated the in vitro effects of GLP-1 on iNKT cells and looked for a functional GLP-1 receptor on these cells.
    The Psoriasis Area and Severity Index improved in both patients following 6 weeks of GLP-1 analogue therapy. This was associated with an alteration in iNKT cell number, with an increased number in the circulation and a decreased number in psoriatic plaques. The GLP-1 receptor was expressed on iNKT cells, and GLP-1 induced a dose-dependent inhibition of iNKT cell cytokine secretion, but not cytolytic degranulation in vitro.
    The clinical effect observed and the direct interaction between GLP-1 and the immune system raise the possibility of therapeutic applications for GLP-1 in inflammatory conditions such as psoriasis.
    Item Type
    Article
    Language
    en
    ISSN
    1432-0428
    ae974a485f413a2113503eed53cd6c53
    10.1007/s00125-011-2232-3
    Scopus Count
    Collections
    St. Columcille's Hospital

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