Granuphilin is activated by SREBP-1c and involved in impaired insulin secretion in diabetic mice.
Cell Metab
; 4(2): 143-54, 2006 Aug.
Article
en En
| MEDLINE
| ID: mdl-16890542
ABSTRACT
Granuphilin is a crucial component of the docking machinery of insulin-containing vesicles to the plasma membrane. Here, we show that the granuphilin promoter is a target of SREBP-1c, a transcription factor that controls fatty acid synthesis, and MafA, a beta cell differentiation factor. Potassium-stimulated insulin secretion (KSIS) was suppressed in islets with adenoviral-mediated overexpression of granuphilin and enhanced in islets with knockdown of granuphilin (in which granuphilin had been knocked down). SREBP-1c and granuphilin were activated in islets from beta cell-specific SREBP-1c transgenic mice, as well as in several diabetic mouse models and normal islets treated with palmitate, accompanied by a corresponding reduction in insulin secretion. Knockdown- or knockout-mediated ablation of granuphilin or SREBP-1c restored KSIS in these islets. Collectively, our data provide evidence that activation of the SREBP-1c/granuphilin pathway is a potential mechanism for impaired insulin secretion in diabetes, contributing to beta cell lipotoxicity.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas de Transporte Vesicular
/
Diabetes Mellitus Experimental
/
Proteína 1 de Unión a los Elementos Reguladores de Esteroles
/
Insulina
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Cell Metab
Asunto de la revista:
METABOLISMO
Año:
2006
Tipo del documento:
Article
País de afiliación:
Japón