A Promoter Genotype and Oxidative Stress Potentially Link Resistin to Human Insulin Resistance

  1. Steve R. Smith,
  2. Fulu Bai,
  3. Chantal Charbonneau,
  4. Lenka Janderová and
  5. George Argyropoulos
  1. 1Pennington Biomedical Research Center, Baton Rouge, Louisiana
  1. Address correspondence and reprint requests to George Argyropoulos or Steve R. Smith, Pennington Biomedical Research Center, 6400 Perkins Rd., Baton Rouge, LA 70808. E-mail: argyrog{at} or or smithsr{at}


Insulin resistance is a component of type 2 diabetes and often precedes pancreatic β-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.


    • Accepted March 19, 2003.
    • Received December 4, 2002.
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