Insulin participates in glucose homeostasis in the body and regulates glucose, protein, and lipid metabolism. Chronic hyperglycemia triggers oxidative stress and the generation of reactive oxygen species (ROS), leading to oxidized insulin variants. Oxidative protein modifications can cause functional changes or altered immunogenicity as known from the context of autoimmune disorders. However, studies on the biological function of native and oxidized insulin on glucose homeostasis and cellular function are lacking. Native insulin showed heterogenous effects on metabolic activity, proliferation, glucose carrier transporter (GLUT) 4, and insulin receptor (INSR) expression, as well as glucose uptake in cell lines of five different human tissues. Diverse ROS compositions produced by different gas plasma approaches enabled the investigations of variously modified insulin (oxIns) with individual oxidative post-translational modification (oxPTM) patterns as identified using high-resolution mass spectrometric analysis. Specific oxIns variants promoted cellular metabolism and proliferation in several cell lines investigated, and nitrogen plasma emission lines could be linked to insulin nitration and elevated glucose uptake. In addition, insulin oxidation modified blood glucose levels in the chicken embryos (in ovo), underlining the importance of assessing protein oxidation and function in health and disease.

中文翻译：

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胰岛素氧化和氧化修饰会改变葡萄糖摄取、细胞代谢和炎症分泌谱


胰岛素参与体内的葡萄糖稳态并调节葡萄糖、蛋白质和脂质代谢。慢性高血糖会触发氧化应激和活性氧 （ROS） 的产生，导致胰岛素氧化变体。氧化蛋白修饰可引起自身免疫性疾病背景下已知的功能改变或免疫原性改变。然而，缺乏关于天然和氧化胰岛素对葡萄糖稳态和细胞功能的生物学功能的研究。天然胰岛素对代谢活性、增殖、葡萄糖载体转运蛋白 （GLUT） 4 和胰岛素受体 （INSR） 表达以及 5 种不同人体组织细胞系中的葡萄糖摄取表现出异质性影响。由不同气体等离子体方法产生的不同 ROS 组成能够研究使用高分辨率质谱分析鉴定的具有个体氧化翻译后修饰 （oxPTM） 模式的各种修饰胰岛素 （oxIns）。在研究的几种细胞系中，特异性 oxIns 变体促进细胞代谢和增殖，氮血浆发射系可能与胰岛素硝化和葡萄糖摄取升高有关。此外，胰岛素氧化改变了鸡胚胎（卵中）的血糖水平，强调了评估蛋白质氧化和功能对健康和疾病的重要性。