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

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, Marian F. Young, Josep Vidal, Ramon Gomis and Rosa Gasa ()
Additional contact information
Rebeca Fernandez-Ruiz: August Pi i Sunyer Biomedical Research Institute (IDIBAPS)
Ainhoa García-Alamán: August Pi i Sunyer Biomedical Research Institute (IDIBAPS)
Yaiza Esteban: August Pi i Sunyer Biomedical Research Institute (IDIBAPS)
Joan Mir-Coll: August Pi i Sunyer Biomedical Research Institute (IDIBAPS)
Berta Serra-Navarro: August Pi i Sunyer Biomedical Research Institute (IDIBAPS)
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
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)
Ramon Gomis: August Pi i Sunyer Biomedical Research Institute (IDIBAPS)
Rosa Gasa: August Pi i Sunyer Biomedical Research Institute (IDIBAPS)

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-19657-1

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