Krogh-Madsen Rikke, Plomgaard Peter, Keller Pernille, Keller Charlotte, Pedersen Bente Klarlund
Department of Infectious Diseases, The Copenhagen Muscle Research Centre, Rigshospitalet, DK-2100 Copenhagen, Denmark.
Am J Physiol Endocrinol Metab. 2004 Feb;286(2):E234-8. doi: 10.1152/ajpendo.00274.2003. Epub 2003 Oct 7.
High circulating levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) 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-alpha may be involved in the pathogenesis of insulin resistance. Therefore, we studied the effect of insulin on IL-6 and TNF-alpha 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-alpha. Muscle and fat biopsies, obtained at 0, 2, 4, and 6 h, were analyzed for IL-6 and TNF-alpha 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-alpha 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-alpha were constant. In conclusion, the finding that insulin stimulates IL-6 and TNF-alpha gene expression in adipose tissue only and inhibits the TNF-alpha production in skeletal muscles suggests a differential regulation of muscle- and adipose tissue-derived IL-6 and TNF-alpha.
高胰岛素血症患者体内白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的循环水平较高。胰岛素可刺激脂肪细胞培养物释放IL-6，并刺激胰岛素抵抗大鼠而非对照大鼠骨骼肌中的IL-6基因表达。此外，TNF-α可能参与胰岛素抵抗的发病机制。因此，我们研究了胰岛素对人骨骼肌和脂肪组织中IL-6和TNF-α基因表达的影响。九名健康年轻志愿者参与了该研究。他们以固定的胰岛素输注速率进行了6小时的高胰岛素正常血糖钳夹，将血糖钳夹在空腹水平。在0、1、2、3、4、5和6小时采集血样，分析其中的IL-6和TNF-α。在0、2、4和6小时获取肌肉和脂肪活检样本，通过实时PCR分析其中的IL-6和TNF-α mRNA。脂肪组织中IL-6 mRNA在2、4和6小时分别增加了11倍、3倍和5倍（方差分析P = 0.027），而胰岛素对骨骼肌没有显著影响。胰岛素刺激期间血浆IL-6升高。脂肪组织中TNF-α mRNA增加了2.4倍、1.4倍和2.2倍（方差分析P = 0.001），而肌肉组织中TNF-α mRNA降低了0.74倍、0.64倍和0.68倍（方差分析P = 0.04）。血浆TNF-α水平保持恒定。总之，胰岛素仅刺激脂肪组织中的IL-6和TNF-α基因表达并抑制骨骼肌中TNF-α的产生这一发现表明，肌肉和脂肪组织来源的IL-6和TNF-α存在差异调节。
