Generation of functional insulin-producing cells in the gut by Foxo1 ablation.
Nat Genet
; 44(4): 406-12, S1, 2012 Mar 11.
Article
en En
| MEDLINE
| ID: mdl-22406641
Restoration of regulated insulin secretion is the ultimate goal of therapy for type 1 diabetes. Here, we show that, unexpectedly, somatic ablation of Foxo1 in Neurog3(+) enteroendocrine progenitor cells gives rise to gut insulin-positive (Ins(+)) cells that express markers of mature ß cells and secrete bioactive insulin as well as C-peptide in response to glucose and sulfonylureas. Lineage tracing experiments showed that gut Ins(+) cells arise cell autonomously from Foxo1-deficient cells. Inducible Foxo1 ablation in adult mice also resulted in the generation of gut Ins(+) cells. Following ablation by the ß-cell toxin streptozotocin, gut Ins(+) cells regenerate and produce insulin, reversing hyperglycemia in mice. The data indicate that Neurog3(+) enteroendocrine progenitors require active Foxo1 to prevent differentiation into Ins(+) cells. Foxo1 ablation in gut epithelium may provide an approach to restore insulin production in type 1 diabetes.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Enteroendocrinas
/
Factores de Transcripción Forkhead
/
Células Neuroendocrinas
/
Insulina
Límite:
Animals
Idioma:
En
Revista:
Nat Genet
Asunto de la revista:
GENETICA MEDICA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos