A δ-cell subpopulation with a pro-ß-cell identity contributes to efficient age-independent recovery in a zebrafish model of diabetes.
Elife
; 112022 01 21.
Article
en En
| MEDLINE
| ID: mdl-35060900
ABSTRACT
Restoring damaged ß-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 ß-cells arising following destruction. We show that most new insulin cells differ from the original ß-cells as they coexpress Somatostatin and Insulin. These bihormonal cells are abundant, functional and able to normalize glycemia. Their formation in response to ß-cell destruction is fast, efficient, and age-independent. Bihormonal cells are transcriptionally close to a subset of δ-cells that we identified in control islets and that are characterized by the expression of somatostatin 1.1 (sst1.1) and by genes essential for glucose-induced Insulin secretion in ß-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 ß-cell destruction. Our findings support the conclusion that sst1.1 δ-cells possess a pro-ß 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Células Secretoras de Somatostatina
/
Diabetes Mellitus Experimental
/
Células Secretoras de Insulina
/
Insulina
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Elife
Año:
2022
Tipo del documento:
Article
País de afiliación:
Bélgica