RSPO1, a potent inducer of pancreatic β cell neogenesis
Inducing the neogenesis of pancreatic insulin-producing β cells holds great promise for diabetes research. However, non-toxic compounds with such activities remain to be discovered. Herein, we report the identification of RSPO1, a key agonist of the Wnt/β-catenin pathway, as an inducer of β cell replication. Specifically, we provide evidence that RSPO1 promotes a significant increase in β cell neogenesis in vitro, ex vivo, and in vivo. Importantly, RSPO1 administration is sufficient to activate Wnt/β-catenin signaling in β cells and counter chemically induced or autoimmune-mediated diabetes. Similarly, an optimized analog of RSPO1, allowing for weekly administration, also prevents diabetes in vivo. Lastly, the treatment of transplanted human islets with RSPO1 induces a significant 2.78-fold increase in human β cell numbers in only 60 days, these cells being functional. Such activities of RSPO1 to promote β cell neogenesis could therefore represent an unprecedented hope in the continued search for diabetes alternative therapies.
Authors
- François Pattou (ORCID: https://orcid.org/0000-0001-8388-3766)
- Patrick Collombat (ORCID: https://orcid.org/0000-0001-8232-1438)
- Samah Rekima
- Magali Plaisant (ORCID: https://orcid.org/0000-0002-9535-3508)
- Benjamin Charles
- Caroline Treins
- Arduino Arduini (ORCID: https://orcid.org/0000-0001-6737-4064)
- Chaïma Ayachi
- Serena Silvano
- Anette Sousa-De-Veiga
- Julien Thévenet (ORCID: https://orcid.org/0000-0001-6873-8640)
- Jérôme Becam
- Paolo Botti
- Gianni Pasquetti
- Loan Tran
- Tiziana Napolitano
- Jacques Mizrahi
- Valentin Lepage (ORCID: https://orcid.org/0000-0002-0123-6256)
- Julie Kerr‐Conte (ORCID: https://orcid.org/0000-0002-7590-1896)
- Hugo Fofo (ORCID: https://orcid.org/0000-0001-8794-0828)
- Benoit Allegrini (ORCID: https://orcid.org/0000-0002-8085-5775)
- Laura Etasse
- Estelle Pichery
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Université Côte d'Azur (FR)
- Centre Hospitalier Universitaire de Lille (FR)
- Institut de Microbiologie de la Méditerranée (FR)
- Institut de Biologie Valrose (FR)
- European Genomic Institute for Diabetes (FR)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2025-05-01
- DOI
- https://doi.org/10.1016/j.xcrm.2025.102126
- Citations
- 1
- Primary Topic
- Pancreatic function and diabetes
- Type
- article
- Field-Weighted Citation Impact
- 2.01
Funders
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Bundesministerium für Bildung und Forschung
- Max-Planck-Gesellschaft