Estrogen Receptor α Regulates ß-Cell Formation During Pancreas Development and Following Injury.
Diabetes
; 64(9): 3218-28, 2015 Sep.
Article
en En
| MEDLINE
| ID: mdl-26015547
ABSTRACT
Identifying pathways for ß-cell generation is essential for cell therapy in diabetes. We investigated the potential of 17ß-estradiol (E2) and estrogen receptor (ER) signaling for stimulating ß-cell generation during embryonic development and in the severely injured adult pancreas. E2 concentration, ER activity, and number of ERα transcripts were enhanced in the pancreas injured by partial duct ligation (PDL) along with nuclear localization of ERα in ß-cells. PDL-induced proliferation of ß-cells depended on aromatase activity. The activation of Neurogenin3 (Ngn3) gene expression and ß-cell growth in PDL pancreas were impaired when ERα was turned off chemically or genetically (ERα(-/-)), whereas in situ delivery of E2 promoted ß-cell formation. In the embryonic pancreas, ß-cell replication, number of Ngn3(+) progenitor cells, and expression of key transcription factors of the endocrine lineage were decreased by ERα inactivation. The current study reveals that E2 and ERα signaling can drive ß-cell replication and formation in mouse pancreas.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Páncreas
/
Conductos Pancreáticos
/
ARN Mensajero
/
Regulación del Desarrollo de la Expresión Génica
/
Receptor alfa de Estrógeno
/
Proliferación Celular
/
Células Secretoras de Insulina
/
Estradiol
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Diabetes
Año:
2015
Tipo del documento:
Article
País de afiliación:
Bélgica