Role of phospholipase D1 in glucose-induced insulin secretion in pancreatic Beta cells.
Exp Mol Med
; 42(6): 456-64, 2010 Jun 30.
Article
en En
| MEDLINE
| ID: mdl-20448441
ABSTRACT
As glucose is known to induce insulin secretion in pancreatic Beta cells, this study investigated the role of a phospholipase D (PLD)-related signaling pathway in insulin secretion caused by high glucose in the pancreatic Beta-cell line MIN6N8. It was found that the PLD activity and PLD1 expression were both increased by high glucose (33.3 mM) treatment. The dominant negative PLD1 inhibited glucose-induced Beta2 expression, and glucose-induced insulin secretion was blocked by treatment with 1-butanol or PLD1-siRNA. These results suggest that high glucose increased insulin secretion through a PLD1-related pathway. High glucose induced the binding of Arf6 to PLD1. Pretreatment with brefeldin A (BFA), an Arf inhibitor, decreased the PLD activity as well as the insulin secretion. Furthermore, BFA blocked the glucose-induced mTOR and p70S6K activation, while mTOR inhibition with rapamycin attenuated the glucose induced Beta2 expression and insulin secretion. Thus, when taken together, PLD1 would appear to be an important regulator of glucose-induced insulin secretion through an Arf6/PLD1/mTOR/p70S6K/ Beta2 pathway in MIN6N8 cells.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Fosfolipasa D
/
Células Secretoras de Insulina
/
Glucosa
/
Insulina
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Exp Mol Med
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Año:
2010
Tipo del documento:
Article