Protection of pancreatic ß-cells against glucotoxicity by short-term treatment with GLP-1.
Biochem Biophys Res Commun
; 459(4): 561-7, 2015 Apr 17.
Article
en En
| MEDLINE
| ID: mdl-25757909
ABSTRACT
Glucagon-like peptide-1 (GLP-1) reduces pancreatic ß-cell apoptosis in type 2 diabetes. Glucotoxiciy is a main cause of ß-cell apoptosis in type 2 diabetes. The aims of this study were to investigate the anti-apoptotic mechanisms of GLP-1 against glucotoxicity and whether physiological short-term treatment with GLP-1 can protect ß-cells from glucotoxicity-induced apoptosis. GLP-1 treatment for only 30 min alleviated high glucose-induced ß-cell apoptosis. The effect of GLP-1 was related with phosphoinositide 3-kinase (PI3K)/AKT-S473 phosphorylation. The increase in pAKT-S473 led to suppression of FoxO-1. GLP-1-induced AKT-S473 activation and FoxO-1 suppression were abolished by the selective inactivation of mTOR complex (mTORC) 2 using small interfering RNA directed towards the rapamycin-insensitive companion of mTOR. The protective effect of GLP-1 on ß-cell apoptosis was also abolished by the selective inactivation of mTORC2. Hence, the protective effect of GLP-1 against glucotoxicity may be mediated by FoxO-1 suppression through the PI3K/mTORC2/AKT-S473 phosphorylation. This report provides evidence that short-term treatment with GLP-1 is beneficial to protect against glucotoxicity-induced ß-cell apoptosis.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Islotes Pancreáticos
/
Péptido 1 Similar al Glucagón
/
Glucosa
Límite:
Animals
Idioma:
En
Año:
2015
Tipo del documento:
Article