Restoring damaged b-cells in diabetic patients by harnessing the plasticity of other pancreatic cells raises the questions of the efficiency of the process and of the functionality of the new Insulin-expressing cells. To overcome the weak regenerative capacity of mammals, we used regeneration-prone zebrafish to study b-cells arising following destruction. We show that most new insulin cells differ from the original b-cells as they coexpress Somatostatin and Insulin. These bihormonal cells are abundant, functional and able to normalize glycemia. Their formation in response to b-cell destruction is fast, efficient and age-independent. Bihormonal cells are transcriptionally close to a subset of d-cells that we identified in control islets and which are characterized by the expression of somatostatin 1.1 (sst1.1) and by genes essential for glucose-induced Insulin secretion in β-cells such as pdx1, slc2a2 and gck. We observed in vivo the conversion of monohormonal sst1.1-expressing cells to sst1.1+ ins+ bihormonal cells following b-cell destruction. Our findings support the conclusion that sst1.1 d-cells possess a pro-b identity enabling them to contribute to the neogenesis of Insulin-producing cells during regeneration. This work unveils that abundant and functional bihormonal cells benefit to diabetes recovery in zebrafish.
RNA sequencing data have been deposited at NCBI GEO
delta-cell conversion to insulin+ somatostatin1.1+ bihormonal cells in a zebrafish model of beta cell destructionNCBI Gene Expression Omnibus, GSE167187.
- Claudio Andrés Carril Pardo
- Arnaud Lavergne
- Laura Massoz
- Marie A Dupont
- David Bergemann
- Jordane Bourdouxhe
- Arnaud Lavergne
- Bernard Peers
- Isabelle Manfroid
- Marianne M Voz
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: All experiments were carried out in compliance with the European Union and Belgian law and with the approval of the ULiège Ethical Committee for experiments with laboratory animals (approval numbers 14-1662, 16-1872, 19-2083, 21-2353).
- Lori Sussel, University of Colorado Anschutz Medical Campus, United States
© 2022, Carril Pardo et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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