Centre of Inflammation and Metabolism and CMRC, Section 7641 Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
Diabetes Metab Res Rev. 2013 Nov;29(8):655-63. doi: 10.1002/dmrr.2441.
Type 2 diabetes mellitus (T2DM) is associated with peripheral insulin resistance, impaired incretin effect, and increased plasma levels of tumour necrosis factor-alpha (TNF-α). Although TNF-α infusion at a dose that induces systemic inflammation in healthy volunteers has been demonstrated to induce peripheral insulin resistance, the influence of this cytokine on the incretin effect is unknown.
We investigated whether systemic inflammation induced by TNF-α infusion in healthy volunteers alters the incretin hormone response to oral and intravenous glucose loads in a crossover study design with ten healthy male volunteers (mean age 24 years, mean body mass index 23.7 kg/m(2) ). The study consisted of four study days: days 1 and 2, 6-h infusion of saline; days 3 and 4, 6-h infusion of TNF-α; days 1 and 3, 4-h oral glucose tolerance test; and days 2 and 4, 4-h corresponding intravenous isoglycaemic glucose tolerance test. Glucose tolerance tests were initiated after 2 h of saline/TNF-α infusion. Plasma concentrations of TNF-α, interleukin 6, glucose, incretin hormones, and cortisol, and serum concentrations of C-peptide and insulin were measured throughout the study days. Insulin sensitivity was estimated by the Matsuda index and homeostasis model assessment of insulin resistance (HOMA-IR). Prehepatic insulin secretion rates were calculated.
TNF-α infusion induced symptoms of systemic inflammation; increased plasma levels of cortisol, TNF-α, and interleukin 6; and increased the HOMA-IR. The secretion of incretin hormones as well as the incretin effect remained unchanged.
In healthy young male volunteers, acute systemic inflammation induced by infusion of TNF-α is associated with insulin resistance with no change in the incretin effect.
2 型糖尿病（T2DM）与外周胰岛素抵抗、肠降血糖素效应受损和肿瘤坏死因子-α（TNF-α）的血浆水平升高有关。虽然在健康志愿者中输注诱导全身炎症的 TNF-α已被证明会引起外周胰岛素抵抗，但这种细胞因子对肠降血糖素效应的影响尚不清楚。
我们通过 10 名健康男性志愿者（平均年龄 24 岁，平均体重指数 23.7 kg/m²）的交叉研究设计，研究了 TNF-α输注在健康志愿者中引起的全身炎症是否会改变口服和静脉葡萄糖负荷后肠降血糖素激素反应。研究包括 4 个研究日：第 1 天和第 2 天，6 小时输注生理盐水；第 3 天和第 4 天，6 小时输注 TNF-α；第 1 天和第 3 天，4 小时口服葡萄糖耐量试验；第 2 天和第 4 天，4 小时相应的静脉等血糖葡萄糖耐量试验。在生理盐水/TNF-α输注 2 小时后开始葡萄糖耐量试验。在整个研究日测量了 TNF-α、白细胞介素 6、葡萄糖、肠降血糖素和皮质醇的血浆浓度，以及 C 肽和胰岛素的血清浓度。通过 Matsuda 指数和稳态模型评估的胰岛素抵抗（HOMA-IR）估计胰岛素敏感性。计算了肝前胰岛素分泌率。
TNF-α 输注引起全身炎症症状；增加了皮质醇、TNF-α 和白细胞介素 6 的血浆水平；并增加了 HOMA-IR。肠降血糖素激素的分泌以及肠降血糖素效应保持不变。
在健康的年轻男性志愿者中，TNF-α 输注引起的急性全身炎症与胰岛素抵抗相关，而肠降血糖素效应没有变化。
