GLP-1 receptor activation improves beta cell function and survival following induction of endoplasmic reticulum stress.
Cell Metab
; 4(5): 391-406, 2006 Nov.
Article
en En
| MEDLINE
| ID: mdl-17084712
ABSTRACT
Perturbation of endoplasmic reticulum (ER) homeostasis impairs insulin biosynthesis, beta cell survival, and glucose homeostasis. We show that a murine model of diabetes is associated with the development of ER stress in beta cells and that treatment with the GLP-1R agonist exendin-4 significantly reduced biochemical markers of islet ER stress in vivo. Exendin-4 attenuated translational downregulation of insulin and improved cell survival in purified rat beta cells and in INS-1 cells following induction of ER stress in vitro. GLP-1R agonists significantly potentiated the induction of ATF-4 by ER stress and accelerated recovery from ER stress-mediated translational repression in INS-1 beta cells in a PKA-dependent manner. The effects of exendin-4 on the induction of ATF-4 were mediated via enhancement of ER stress-stimulated ATF-4 translation. Moreover, exendin-4 reduced ER stress-associated beta cell death in a PKA-dependent manner. These findings demonstrate that GLP-1R signaling directly modulates the ER stress response leading to promotion of beta cell adaptation and survival.
Buscar en Google
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Péptidos
/
Estrés Fisiológico
/
Ponzoñas
/
Receptores de Glucagón
/
EIF-2 Quinasa
/
Retículo Endoplásmico
/
Células Secretoras de Insulina
/
Factor de Transcripción Activador 4
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Cell Metab
Asunto de la revista:
METABOLISMO
Año:
2006
Tipo del documento:
Article
País de afiliación:
Canadá