Autor: |
Cardellini, Marina, Perego, Lucia, D'Adamo, Monica, Marini, Maria Adelaide, Procopio, Cristina, Hribal, Marta Letizia, Andreozzi, Francesco, Frontoni, Simona, Giacomelli, Maurizio, Paganelli, Michele, Pontiroli, Antonio E., Lauro, Renato, Folli, Franco, Sesti, Giorgio |
Předmět: |
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Zdroj: |
Diabetes Care; Aug2005, Vol. 28 Issue 8, p2007-2012, 6p, 3 Charts, 1 Graph |
Abstrakt: |
OBJECTIVE -- The C-174G promoter polymorphism of the interleukin ([L)-6 gene was found to influence transcriptional activity and plasma IL-6 levels in humans. We addressed the question of whether the C-174G IL-6 polymorphism contributes to variation of insulin sensitivity. RESEARCH DESIGN AND METHODS -- Two cohorts of subjects were genotyped. Cohort 1 includes 275 nondiabetic subjects who underwent a euglycemic-hyperinsulinemic clamp. Cohort 2 includes 77 patients with morbid obesity who underwent laparoscopic adjustable gastric banding (LAGB). RESULTS -- The genotypes were consistent with Hardy-Weinberg equilibrium proportions. In cohort 1, insulin sensitivity was reduced in carriers of the -174G/G genotype as compared with subjects carrying the C allele (P = 0.004). Carriers of -174G/G displayed significantly higher plasma IL-6 levels in comparison with carriers of the C allele. In a stepwise linear regression analysis, the C-174G polymorphism was independently associated with insulin sensitivity; however, after inclusion of plasma IL-6 concentrations, the polymorphism was excluded from the model explaining insulin sensitivity variability, thus suggesting that the polymorphism was affecting insulin sensitivity by regulating IL-6 plasma levels. IL-6 mRNA levels were measured by real-time RT-PCR in subcutaneous fat obtained from obese patients of cohort 2 during LAGB. Carriers of -174G/G showed increased IL-6 expression compared with subjects carrying the C allele (P = 0.04). There was a significant correlation between adipose IL-6 mRNA expression and insulin resistance assessed by homeostasis model assessment (ρ = 0.28, P = 0.014). CONCLUSIONS -- These results indicate that the -174G/G genotype of the IL-6 gene may contribute to variations in insulin sensitivity. [ABSTRACT FROM AUTHOR] |
Databáze: |
Complementary Index |
Externí odkaz: |
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