Lipid hydroperoxide-derived insulin resistance and its inhibition by pyridoxamine in skeletal muscle cells.

IF 1.6 4区医学 Q4 TOXICOLOGY

Toxicological Research Pub Date : 2022-11-29 eCollection Date: 2023-01-01 DOI:10.1007/s43188-022-00155-z

Seon Hwa Lee, Mizuki Tsutsui, Atsushi Matsunaga, Tomoyuki Oe

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引用次数: 1

Abstract

Oxidative stress is strongly associated with the onset and/or progression of diabetes. Under conditions of oxidative stress, lipid hydroperoxides are decomposed to reactive aldehydes that have been reported to induce insulin resistance by modifying proteins involved in insulin signaling. Pyridoxamine (PM) can inhibit the formation of advanced glycation/lipoxidation end products by scavenging reactive carbonyl species. Thus, PM has emerged as a promising drug candidate for various chronic conditions, including diabetic complications. In this study, L6 skeletal muscle cells were treated with 4-oxo-2(E)-nonenal (ONE), one of the most abundant and reactive lipid-derived aldehydes. Cellular insulin resistance was assessed by measuring insulin-stimulated glucose uptake using 2-deoxyglucose. ONE induced a time- and dose-dependent decrease in glucose uptake. Liquid chromatography/electrospray ionization-mass spectrometry analysis of the reaction between ONE and insulin receptor substrate 1 (IRS1) lysate identified multiple modifications that could disturb the interaction between IRS1 and activated IR, leading to insulin resistance. Pretreatment of the cells with PM restored the ONE-induced decrease in glucose uptake. Concomitantly, the formation of PM-ONE adducts in cell culture medium was increased in a PM-dose dependent manner. PM can therefore prevent lipid hydroperoxide-derived insulin resistance by quenching ONE.

Supplementary information: The online version contains supplementary material available at 10.1007/s43188-022-00155-z.

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骨骼肌细胞中脂质氢过氧化物衍生的胰岛素抵抗及其对吡多胺的抑制作用

氧化应激与糖尿病的发生和/或发展密切相关。在氧化应激条件下，脂质氢过氧化物会分解成活性醛，据报道，活性醛会改变参与胰岛素信号传导的蛋白质，从而诱发胰岛素抵抗。吡多胺（PM）可以通过清除活性羰基来抑制高级糖化/脂氧化终产物的形成。因此，吡多胺已成为治疗包括糖尿病并发症在内的各种慢性疾病的一种有前途的候选药物。在这项研究中，用 4-oxo-2(E)-nonenal (ONE) 处理 L6 骨骼肌细胞。通过使用 2-脱氧葡萄糖测量胰岛素刺激的葡萄糖摄取量来评估细胞的胰岛素抵抗。ONE诱导的葡萄糖摄取量的下降与时间和剂量有关。对 ONE 与胰岛素受体底物 1（IRS1）裂解物之间反应的液相色谱/电喷雾离子化-质谱分析发现了多种修饰，这些修饰可能会干扰 IRS1 与活化的 IR 之间的相互作用，从而导致胰岛素抵抗。用 PM 对细胞进行预处理可恢复 ONE 诱导的葡萄糖摄取减少。同时，细胞培养基中 PM-ONE 加合物的形成以 PM 剂量依赖性的方式增加。因此，PM 可以通过淬灭 ONE 来防止脂质过氧化氢衍生的胰岛素抵抗：在线版本包含补充材料，可查阅 10.1007/s43188-022-00155-z。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Toxicological Research TOXICOLOGY-

CiteScore

4.20

自引率

4.30%

发文量

期刊介绍： Toxicological Research is the official journal of the Korean Society of Toxicology. The journal covers all areas of Toxicological Research of chemicals, drugs and environmental agents affecting human and animals, which in turn impact public health. The journal’s mission is to disseminate scientific and technical information on diverse areas of toxicological research. Contributions by toxicologists, molecular biologists, geneticists, biochemists, pharmacologists, clinical researchers and epidemiologists with a global view on public health through toxicological research are welcome. Emphasis will be given to articles providing an understanding of the toxicological mechanisms affecting animal, human and public health. In the case of research articles using natural extracts, detailed information with respect to the origin, extraction method, chemical profiles, and characterization of standard compounds to ensure the reproducible pharmacological activity should be provided.