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Wisp1 is a circulating factor that stimulates proliferation of adult mouse and human beta cells

Author

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  • Rebeca Fernandez-Ruiz

    (August Pi i Sunyer Biomedical Research Institute (IDIBAPS)
    Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM)
    University of Barcelona)

  • Ainhoa García-Alamán

    (August Pi i Sunyer Biomedical Research Institute (IDIBAPS)
    Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM))

  • Yaiza Esteban

    (August Pi i Sunyer Biomedical Research Institute (IDIBAPS)
    Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM))

  • Joan Mir-Coll

    (August Pi i Sunyer Biomedical Research Institute (IDIBAPS)
    University of Barcelona)

  • Berta Serra-Navarro

    (August Pi i Sunyer Biomedical Research Institute (IDIBAPS)
    University of Barcelona)

  • Marta Fontcuberta-PiSunyer

    (August Pi i Sunyer Biomedical Research Institute (IDIBAPS))

  • Christophe Broca

    (CHU Montpellier, Laboratory of Cell Therapy for Diabetes (LTCD), Hospital St-Eloi)

  • Mathieu Armanet

    (CHU Montpellier, Laboratory of Cell Therapy for Diabetes (LTCD), Hospital St-Eloi)

  • Anne Wojtusciszyn

    (CHU Montpellier, Laboratory of Cell Therapy for Diabetes (LTCD), Hospital St-Eloi
    Lausanne University Hospital)

  • Vardit Kram

    (Molecular Biology of Bones and Teeth Section, NIDCR, National Institutes of Health)

  • Marian F. Young

    (Molecular Biology of Bones and Teeth Section, NIDCR, National Institutes of Health)

  • Josep Vidal

    (August Pi i Sunyer Biomedical Research Institute (IDIBAPS)
    Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM)
    Department of Endocrinology and Nutrition, Hospital Clinic of Barcelona)

  • Ramon Gomis

    (August Pi i Sunyer Biomedical Research Institute (IDIBAPS)
    Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM)
    University of Barcelona
    Universitat Oberta de Catalunya (UOC))

  • Rosa Gasa

    (August Pi i Sunyer Biomedical Research Institute (IDIBAPS)
    Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM))

Abstract

Expanding the mass of pancreatic insulin-producing beta cells through re-activation of beta cell replication has been proposed as a therapy to prevent or delay the appearance of diabetes. Pancreatic beta cells exhibit an age-dependent decrease in their proliferative activity, partly related to changes in the systemic environment. Here we report the identification of CCN4/Wisp1 as a circulating factor more abundant in pre-weaning than in adult mice. We show that Wisp1 promotes endogenous and transplanted adult beta cell proliferation in vivo. We validate these findings using isolated mouse and human islets and find that the beta cell trophic effect of Wisp1 is dependent on Akt signaling. In summary, our study reveals the role of Wisp1 as an inducer of beta cell replication, supporting the idea that the use of young blood factors may be a useful strategy to expand adult beta cell mass.

Suggested Citation

  • Rebeca Fernandez-Ruiz & Ainhoa García-Alamán & Yaiza Esteban & Joan Mir-Coll & Berta Serra-Navarro & Marta Fontcuberta-PiSunyer & Christophe Broca & Mathieu Armanet & Anne Wojtusciszyn & Vardit Kram &, 2020. "Wisp1 is a circulating factor that stimulates proliferation of adult mouse and human beta cells," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19657-1
    DOI: 10.1038/s41467-020-19657-1
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