Influence of TNF-α and IL-6 infusions on insulin sensitivity and expression of IL-18 in humans
Influence of TNF-α and IL-6 infusions on insulin sensitivity and expression of IL-18 in humans
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DOI：
10.1152/ajpendo.00471.2005
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发表时间：
2006-07-01
影响因子：
5.1
通讯作者：
Pedersen, Bente K.
中科院分区：
文献类型：
--
作者：
Krogh-Madsen, Rikke;Plomgaard, Peter;Pedersen, Bente K.
炎症与胰岛素抵抗相关，肿瘤坏死因子（TNF）-α和白细胞介素（IL）-6都可能影响葡萄糖摄取。TNF诱导胰岛素抵抗，而IL-6的作用是有争议的。在流行病学研究中，高血浆IL-18水平与胰岛素抵抗相关。我们研究了TNF和IL-6对骨骼肌和脂肪组织中IL-18基因表达的影响。9名人类志愿者接受了3次连续干预，接受重组人（rh）IL-6、rhTNF和生理盐水输注。在正常血糖高胰岛素钳夹（20 mU（.）min（-1）（.）kg（-1）），在IL-6-TNF-盐水输注后1 h开始。在血浆、肌肉和脂肪活检中测量细胞因子反应。在细胞因子输注期间，TNF和IL-6的血浆浓度分别增加了10倍和38倍。全身胰岛素介导的葡萄糖摄取在TNF输注期间显著降低，但在IL-6输注期间保持不变。TNF诱导IL-18基因在肌肉组织中的表达，但不是在脂肪组织中，而IL-6输注对IL-18基因在任一组织中的表达没有影响。我们的结论是，TNF诱导的胰岛素抵抗的全身葡萄糖摄取与肌肉组织中IL-18基因表达的增加，表明TNF和IL-18相互作用，两者可能有重要的调节作用，在胰岛素抵抗的发病机制。
Inflammation is associated with insulin resistance, and both tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 may affect glucose uptake. TNF induces insulin resistance, whereas the role of IL-6 is controversial. High plasma levels of IL-18 are associated with insulin resistance in epidemiological studies. We investigated the effects of TNF and IL-6 on IL-18 gene expression in skeletal muscle and adipose tissue. Nine human volunteers underwent three consecutive interventions, receiving an infusion of recombinant human (rh)IL-6, rhTNF, and saline. Insulin sensitivity was assessed by measurement of whole body glucose uptake with the stable isotope tracer method during a euglycemic hyperinsulinemic clamp (20 mU (.) min(-1) (.) kg(-1)), which was initiated 1 h after the IL-6-TNF-saline infusion. Cytokine responses were measured in plasma, muscle, and fat biopsies. Plasma concentrations of TNF and IL-6 increased 10- and 38-fold, respectively, during the cytokine infusions. Whole body insulin-mediated glucose uptake was significantly reduced during TNF infusion but remained unchanged during IL-6 infusion. TNF induced IL-18 gene expression in muscle tissue, but not in adipose tissue, whereas IL-6 infusion had no effect on IL-18 gene expression in either tissue. We conclude that TNF-induced insulin resistance of whole body glucose uptake is associated with increased IL-18 gene expression in muscle tissue, indicating that TNF and IL-18 interact, and both may have important regulatory roles in the pathogenesis of insulin resistance.