Constitutive activation of β-catenin in conventional dendritic cells increases the insulin reserve to ameliorate the development of type 2 diabetes in mice

Claire E. MacDougall, Elizabeth G. Wood, Antonia Solomou, Valeria Scagliotti, Makoto Mark Taketo, Carles Gaston-Massuet, Federica M. Marelli-Berg, Marika Charalambous, M. Paula Longhi

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    Abstract

    β-Cell failure is central to the development of type 2 diabetes mellitus (T2DM). Dysregulation of metabolic and inflammatory processes during obesity contributes to the loss of islet function and impaired β-cell insulin secretion. Modulating the immune system, therefore, has the potential to ameliorate diseases. We report that inducing sustained expression of β-catenin in conventional dendritic cells (cDCs) provides a novel mechanism to enhance β-cell insulin secretion. Intriguingly, cDCs with constitutively activated β-catenin induced islet expansion by increasing β-cell proliferation in a model of diet-induced obesity. We further found that inflammation in these islets was reduced. Combined, these effects improved β-cell insulin secretion, suggesting a unique compensatory mechanism driven by cDCs to generate a greater insulin reserve in response to obesity-induced insulin resistance. Our findings highlight the potential of immune modulation to improve β-cell mass and function in T2DM.

    Original languageEnglish (US)
    Pages (from-to)1473-1484
    Number of pages12
    JournalDiabetes
    Volume68
    Issue number7
    DOIs
    StatePublished - Jan 1 2019

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    ASJC Scopus subject areas

    • Internal Medicine
    • Endocrinology, Diabetes and Metabolism

    Cite this

    MacDougall, C. E., Wood, E. G., Solomou, A., Scagliotti, V., Taketo, M. M., Gaston-Massuet, C., Marelli-Berg, F. M., Charalambous, M., & Longhi, M. P. (2019). Constitutive activation of β-catenin in conventional dendritic cells increases the insulin reserve to ameliorate the development of type 2 diabetes in mice. Diabetes, 68(7), 1473-1484. https://doi.org/10.2337/db18-1243