A promoter genotype and oxidative stress potentially link resistin to human insulin resistance.
Diabetes
; 52(7): 1611-8, 2003 Jul.
Article
em En
| MEDLINE
| ID: mdl-12829623
ABSTRACT
Insulin resistance is a component of type 2 diabetes and often precedes pancreatic beta-cell failure. Contributing factors include obesity and a central pattern of fat accumulation with a strong genetic component. The adipocyte secreted hormone resistin has been proposed as a link between the adipocyte and insulin resistance by inhibition of insulin-stimulated glucose uptake and/or blocking adipocyte differentiation. Here we report that the G/G genotype of a single nucleotide polymorphism (SNP) in the promoter of the human resistin gene, -180C>G, had significantly increased basal promoter activity in adipocytes. These data were recapitulated in vivo, where G/G homozygotes had significantly higher resistin mRNA levels in human abdominal subcutaneous fat. A significant interaction was also found between the -180C>G SNP, a marker of oxidative stress (NAD[P]H quinone oxidoreductase mRNA) and homeostasis model assessment of insulin resistance. In addition, resistin mRNA was positively and independently correlated with insulin resistance and hepatic fat as measured by liver X-ray attenuation. These data implicate resistin in the pathophysiology of the human insulin resistance syndrome, an effect mediated by the -180C>G promoter SNP and potentially cellular oxidative stress.
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Base de dados:
MEDLINE
Assunto principal:
Resistência à Insulina
/
Regiões Promotoras Genéticas
/
Estresse Oxidativo
/
Polimorfismo de Nucleotídeo Único
/
Peptídeos e Proteínas de Sinalização Intercelular
/
Hormônios Ectópicos
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article