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

Research output: Contribution to journalArticle

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

Original languageEnglish
Pages (from-to)1473-1484
Number of pages12
Issue number7
Publication statusPublished - 1 Jan 2019

King's Authors


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.

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