A common variant in TFB1M is associated with reduced insulin secretion and increased future risk of type 2 diabetes.
Cell Metab
; 13(1): 80-91, 2011 Jan 05.
Article
en En
| MEDLINE
| ID: mdl-21195351
ABSTRACT
Type 2 diabetes (T2D) evolves when insulin secretion fails. Insulin release from the pancreatic ß cell is controlled by mitochondrial metabolism, which translates fluctuations in blood glucose into metabolic coupling signals. We identified a common variant (rs950994) in the human transcription factor B1 mitochondrial (TFB1M) gene associated with reduced insulin secretion, elevated postprandial glucose levels, and future risk of T2D. Because islet TFB1M mRNA levels were lower in carriers of the risk allele and correlated with insulin secretion, we examined mice heterozygous for Tfb1m deficiency. These mice displayed lower expression of TFB1M in islets and impaired mitochondrial function and released less insulin in response to glucose in vivo and in vitro. Reducing TFB1M mRNA and protein in clonal ß cells by RNA interference impaired complexes of the mitochondrial oxidative phosphorylation system. Consequently, nutrient-stimulated ATP generation was reduced, leading to perturbed insulin secretion. We conclude that a deficiency in TFB1M and impaired mitochondrial function contribute to the pathogenesis of T2D.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Proteínas Mitocondriales
/
Diabetes Mellitus Tipo 2
/
Proteínas de Unión al ADN
/
Insulina
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
Cell Metab
Asunto de la revista:
METABOLISMO
Año:
2011
Tipo del documento:
Article
País de afiliación:
Suecia