Fatty acid-binding protein 4 impairs the insulin-dependent nitric oxide pathway in vascular endothelial cells.
Cardiovasc Diabetol
; 11: 72, 2012 Jun 18.
Article
en En
| MEDLINE
| ID: mdl-22709426
ABSTRACT
BACKGROUND:
Recent studies have shown that fatty acid-binding protein 4 (FABP4) plasma levels are associated with impaired endothelial function in type 2 diabetes (T2D). In this work, we analysed the effect of FABP4 on the insulin-mediated nitric oxide (NO) production by endothelial cells in vitro.METHODS:
In human umbilical vascular endothelial cells (HUVECs), we measured the effects of FABP4 on the insulin-mediated endothelial nitric oxide synthase (eNOS) expression and activation and on NO production. We also explored the impact of exogenous FABP4 on the insulin-signalling pathway (insulin receptor substrate 1 (IRS1) and Akt).RESULTS:
We found that eNOS expression and activation and NO production are significantly inhibited by exogenous FABP4 in HUVECs. FABP4 induced an alteration of the insulin-mediated eNOS pathway by inhibiting IRS1 and Akt activation. These results suggest that FABP4 induces endothelial dysfunction by inhibiting the activation of the insulin-signalling pathway resulting in decreased eNOS activation and NO production.CONCLUSION:
These findings provide a mechanistic linkage between FABP4 and impaired endothelial function in diabetes, which leads to an increased cardiovascular risk.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
Proteínas de Unión a Ácidos Grasos
/
Células Endoteliales de la Vena Umbilical Humana
/
Insulina
/
Óxido Nítrico
Límite:
Humans
Idioma:
En
Revista:
Cardiovasc Diabetol
Asunto de la revista:
ANGIOLOGIA
/
CARDIOLOGIA
/
ENDOCRINOLOGIA
Año:
2012
Tipo del documento:
Article
País de afiliación:
España