Zavaroni I, Numeroso F, Dongiovanni P, Ardigò D, Valenti L, Fracanzani A l, Valtuena S, Delsignore R, Fargion S, Reaven G M
Department of Internal Medicine and Biomedical Sciences, Parma University, Italy.
Metabolism. 2003 Dec;52(12):1593-6. doi: 10.1016/s0026-0495(03)00329-9.
To address the potential role that tumor necrosis factor-alpha (TNF-alpha) might play in modulation of insulin resistance in healthy, nondiabetic individuals, we compared plasma TNF-alpha and soluble TNF-alpha receptor 2 (sTNF-R2) concentrations, as well as TNF-alpha polymorphisms, in 94 healthy individuals, stratified into insulin-resistant (IR) and insulin-sensitive (IS) groups based on their plasma insulin concentrations 120 minutes after oral glucose on 2 occasions (1993 and 2000). The IR group (n = 50; 29 men and 21 women) was in the upper quartile and the IS group (n = 44; 24 men and 20 women) in the lowest quartile of the distribution of post-glucose challenge insulin concentrations in a large unselected population (>50 v <23 microU/mL). The IR group had significantly higher values for body mass index, waist-to-hip girth, fasting and post-glucose challenge insulin concentrations, and fasting triglyceride concentrations, and lower high-density lipoprotein cholesterol concentrations as compared to the IS group. Despite the fact that they were relatively more obese, and insulin-resistant, plasma concentrations of TNF-alpha were similar in the IR (1.6 +/- 0.6 pg/mL) and IS (1.7 +/- 0.6 pg/mL) groups, as were the concentrations (5.4 +/- 1.4 v 5.8 +/- 2.0 pg/mL) of sTNF-R2. Furthermore, TNF-alpha polymorphisms (detected by polymerase chain reaction [PCR]) were similar in the 2 groups, with essentially identical allelic frequencies of the 238 (10.3% v 9.4%) and 308 polymorphisms (17.9% v 18.7%). In conclusion, plasma TNF-alpha and sTNF-R2 concentrations, as well as TNF-alpha gene polymorphisms, were not different in healthy volunteers stratified into IR and IS groups on the basis of their plasma insulin response to an oral glucose challenge. Given these data, it does not appear that differences in TNF-alpha activity contribute to the marked variations in insulin action that occur in healthy individuals.
为了探究肿瘤坏死因子-α（TNF-α）在健康非糖尿病个体胰岛素抵抗调节中可能发挥的潜在作用，我们比较了94名健康个体的血浆TNF-α和可溶性TNF-α受体2（sTNF-R2）浓度以及TNF-α基因多态性。这些个体在1993年和2000年分两次口服葡萄糖后120分钟，根据其血浆胰岛素浓度分为胰岛素抵抗（IR）组和胰岛素敏感（IS）组。IR组（n = 50；29名男性和21名女性）处于大型未筛选人群（>50 v <23微单位/毫升）葡萄糖激发后胰岛素浓度分布的上四分位数，IS组（n = 44；24名男性和20名女性）处于最低四分位数。与IS组相比，IR组的体重指数、腰臀围、空腹及葡萄糖激发后胰岛素浓度和空腹甘油三酯浓度显著更高，高密度脂蛋白胆固醇浓度更低。尽管IR组相对更肥胖且有胰岛素抵抗，但IR组（1.6±0.6皮克/毫升）和IS组（1.7±0.6皮克/毫升）的血浆TNF-α浓度相似，sTNF-R2浓度也相似（5.4±1.4 v 5.8±2.0皮克/毫升）。此外，两组的TNF-α基因多态性（通过聚合酶链反应[PCR]检测）相似，238（10.3% v 9.4%）和308多态性的等位基因频率基本相同。总之，根据口服葡萄糖激发后的血浆胰岛素反应分为IR组和IS组的健康志愿者中，血浆TNF-α和sTNF-R2浓度以及TNF-α基因多态性并无差异。基于这些数据，TNF-α活性的差异似乎并未导致健康个体胰岛素作用的显著变化。
