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gene expression in human subcutaneous adipose tissue
Department of Infectious Diseases, The Copenhagen Muscle Research Centre, Rigshospitalet, DK-2100 Copenhagen, Denmark
Submitted 18 June 2003 ; accepted in final form 30 September 2003
High circulating levels of interleukin-6 (IL-6) and tumor necrosis factor-
(TNF-) are found in patients with hyperinsulinemia. Insulin stimulates release of IL-6 from adipocyte cultures, and it stimulates IL-6 gene expression in insulin-resistant, but not control, rat skeletal muscle. In addition, TNF- may be involved in the pathogenesis of insulin resistance. Therefore, we studied the effect of insulin on IL-6 and TNF- gene expression in human skeletal muscle and adipose tissue. Nine healthy young volunteers participated in the study. They underwent a 6-h hyperinsulinemic euglycemic clamp at a fixed insulin infusion rate, with blood glucose clamped at fasting level. Blood samples drawn at 0, 1, 2, 3, 4, 5, and 6 h were analyzed for IL-6 and TNF-. Muscle and fat biopsies, obtained at 0, 2, 4, and 6 h, were analyzed for IL-6 and TNF- mRNA with real-time PCR. IL-6 mRNA increased 11-, 3-, and 5-fold at 2, 4, and 6 h, respectively, in adipose tissue (ANOVA P = 0.027), whereas there was no significant effect of insulin on skeletal muscles. Plasma IL-6 increased during insulin stimulation. TNF- mRNA increased 2.4-, 1.4-, and 2.2-fold in adipose tissue (ANOVA P = 0.001) and decreased 0.74-, 0.64-, and 0.68-fold in muscle tissue (ANOVA P = 0.04). Plasma levels of TNF- were constant. In conclusion, the finding that insulin stimulates IL-6 and TNF- gene expression in adipose tissue only and inhibits the TNF- production in skeletal muscles suggests a differential regulation of muscle- and adipose tissue-derived IL-6 and TNF-.
cytokines; euglycemic clamp
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