Regulation of PKD by the MAPK p38delta in insulin secretion and glucose homeostasis.
Cell
; 136(2): 235-48, 2009 Jan 23.
Article
en En
| MEDLINE
| ID: mdl-19135240
ABSTRACT
Dysfunction and loss of insulin-producing pancreatic beta cells represent hallmarks of diabetes mellitus. Here, we show that mice lacking the mitogen-activated protein kinase (MAPK) p38delta display improved glucose tolerance due to enhanced insulin secretion from pancreatic beta cells. Deletion of p38delta results in pronounced activation of protein kinase D (PKD), the latter of which we have identified as a pivotal regulator of stimulated insulin exocytosis. p38delta catalyzes an inhibitory phosphorylation of PKD1, thereby attenuating stimulated insulin secretion. In addition, p38delta null mice are protected against high-fat-feeding-induced insulin resistance and oxidative stress-mediated beta cell failure. Inhibition of PKD1 reverses enhanced insulin secretion from p38delta-deficient islets and glucose tolerance in p38delta null mice as well as their susceptibility to oxidative stress. In conclusion, the p38delta-PKD pathway integrates regulation of the insulin secretory capacity and survival of pancreatic beta cells, pointing to a pivotal role for this pathway in the development of overt diabetes mellitus.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteína Quinasa C
/
Proteína Quinasa 13 Activada por Mitógenos
/
Células Secretoras de Insulina
/
Insulina
Límite:
Animals
Idioma:
En
Revista:
Cell
Año:
2009
Tipo del documento:
Article
País de afiliación:
Suiza