Postgraduate Studies and Research Section, School of Medicine National Polytechnique Institute, Mexico Distrito Federal, Mexico.
Horm Metab Res. 2011 Oct;43(11):748-53. doi: 10.1055/s-0031-1286305. Epub 2011 Oct 18.
Obesity and its associated disorders constitute a growing epidemic across the world. Numerous studies have demonstrated the presence of systemic oxidative stress in patients with obesity. In this study, we show the effects of oxidative stress present in the blood from obese patients on recombinant human insulin. Insulin was incubated with whole blood (WB) from overweight subjects (OW), obese 1 patients (O1), or normal weight volunteers (NW) (n=16 for each group). Whole blood from OW and O1, unlike WB from NW, increased the carbonyl content of insulin; however, only whole blood from O1 patients increased the amount of formazan present in the hormone. Interestingly, the incubation of insulin with WB from O1 provoked a decrease in the hypoglycemic activity of the hormone (18%), an effect due to insulin polymerization. In addition, we showed that the formation of the insulin polymer generated the formation of new epitopes and the development of a new immunogenicity. These observations show that oxidative stress present in the WB of O1 patients can result in abolition of the biological activity of insulin and contribute to the development of an immune response to the hormone.
肥胖及其相关疾病在全球范围内构成了一个日益严重的流行问题。大量研究表明，肥胖患者存在系统性氧化应激。在这项研究中，我们展示了肥胖患者血液中存在的氧化应激对重组人胰岛素的影响。将胰岛素与超重受试者（OW）、肥胖 1 型患者（O1）或正常体重志愿者（NW）的全血（WB）（每组 16 人）孵育。与 NW 的 WB 不同，OW 和 O1 的全血增加了胰岛素的羰基含量；然而，只有 O1 患者的全血增加了激素中存在的甲臜量。有趣的是，将胰岛素与 O1 的 WB 孵育会导致激素的降血糖活性降低（18%），这是由于胰岛素聚合引起的。此外，我们表明，胰岛素聚合物的形成导致了新表位的形成和新的免疫原性的发展。这些观察结果表明，O1 患者 WB 中存在的氧化应激可导致胰岛素生物活性的丧失，并有助于对激素产生免疫反应。
