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在氧化应激条件下,与糖尿病患者的血液体外孵育对人胰岛素的化学和功能变化。

Chemical and functional changes of human insulin by in vitro incubation with blood from diabetic patients in oxidative stress.

机构信息

General Hospital, Nacional Medical Center La Raza, Mexican Institute for Social Security, Mexico City, Mexico.

出版信息

Metabolism. 2010 Jul;59(7):935-42. doi: 10.1016/j.metabol.2009.10.013.

Abstract

Oxidative stress damage to biomolecules has been implicated in several diseases including diabetes mellitus. In the present study, we investigated the effect of oxidative stress in whole blood (WB) from diabetic patients (n = 60) on recombinant human insulin. Insulin was incubated with WB obtained from diabetic patients (DP) who had hyperglycemia (>300 mg/dL) or from 41 healthy volunteers (HV). Whole blood of DP, unlike WB of HV, induced higher values of formazan (142%), dityrosines (279%), and carbonyls (58%) in the insulin residues. Interestingly, the insulin modified by WB of DP showed less hypoglycemic activity in rat (30%) in comparison with insulin incubated with WB of HV. The incubation of insulin in WB from DP induces chemical changes in insulin and a decrease in its biological activity, events that might be associated with the high levels of oxidative stress markers found in the plasma of these patients.

摘要

生物分子的氧化应激损伤与包括糖尿病在内的多种疾病有关。在本研究中,我们研究了糖尿病患者(n = 60)全血(WB)中的氧化应激对重组人胰岛素的影响。胰岛素与来自高血糖(>300mg/dL)的糖尿病患者(DP)或 41 名健康志愿者(HV)的 WB 孵育。与 HV 的 WB 不同,DP 的 WB 诱导胰岛素残基中更高的甲臜(142%)、二酪氨酸(279%)和羰基(58%)值。有趣的是,与在 HV 的 WB 中孵育的胰岛素相比,由 DP 的 WB 修饰的胰岛素在大鼠中的降血糖活性降低了 30%。在 DP 的 WB 中孵育胰岛素会导致胰岛素发生化学变化并降低其生物活性,这些事件可能与这些患者血浆中发现的高水平氧化应激标志物有关。

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