Exenatide substantially improves proinsulin conversion and cell survival that augment Ins2+/Akita beta cell function.
Mol Cell Endocrinol
; 439: 297-307, 2017 01 05.
Article
en En
| MEDLINE
| ID: mdl-27658750
Proinsulin folding imperfections cause extensive beta-cell defects known in diabetes. Here, we investigated whether exenatide can alleviate such defects in proinsulin conversion, beta-cell survival, and insulin secretion, in the Ins2+/Akita beta-cells that have a spontaneous mutation (Cys 96 Tyr) in the insulin 2 gene caused dominant negative misfolding problem. 15 or 120 min exenatide administration substantially improves glucose-stimulated insulin secretion, marked in the secreted insulin levels and proinsulin/insulin ratio. This improvement is mainly due to enhanced conversion of proinsulin to insulin, having nothing to do with the prohormone convertase PC1/3 and PC2 levels. The 15 min improvement is calcium-independent. The 120 min improvement is linked to calcium and/or cAMP dependent mechanisms. This efficacy is validated during longer treatment and in Akita islets. Exenatide improves Ins2+/Akita beta-cell survival and Akita mouse's glucose tolerance. The results suggest a potential of incretin mimetics in alleviating defective proinsulin conversion and other proinsulin misfolding consequences.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Péptidos
/
Proinsulina
/
Ponzoñas
/
Células Secretoras de Insulina
Límite:
Animals
Idioma:
En
Revista:
Mol Cell Endocrinol
Año:
2017
Tipo del documento:
Article
Pais de publicación:
Irlanda