持续的辐射后骨肌肉蛋白和非人类灵长类动物的胰岛素敏感性变化
Jingyun Lee1, Xiaofei Chen1, Katherine M Fanning2
1Department of Internal Medicine, Section on Molecular Medicine.
Radiation research
|March 7, 2025
概括
全身辐射会导致非人类灵长类动物的骨肌持续抗胰岛素,导致2型糖尿病. 这种功能障碍涉及胰岛素信号受损和肌肉组织中线粒体动态变化.
科学领域:
- 内分泌学 在内分泌学.
- 辐射生物学 辐射生物学
- 肌肉生理学 肌肉生理学
背景情况:
- 全身辐射与癌症幸存者和动物模型中糖尿病发病率的增加有关.
- 2型糖尿病照射后发生在没有肥胖的情况下,涉及骨肌肉功能障碍.
- 骨肌肉对于葡萄糖的处理和每分钟的葡萄糖调节至关重要.
研究的目的:
- 研究全身辐射对骨肌肉胰岛素敏感性的持续影响.
- 确定辐射诱导的骨肌肉胰岛素抵抗的基础分子机制.
主要方法:
- 从对照和辐射的雄性 rhesus macaques 进行骨肌肉分析,辐射后4年 (6.5 Gy).
- 评估骨肌肉中基础和胰岛素刺激的受体激活.
- 蛋白质组学分析 (shotgun蛋白质组学,免疫阻塞) 来识别蛋白质变化,包括像硫化这样的翻译后修改.
- 评估线粒体动力学标志物 (裂变和融合).
主要成果:
- 被辐射的骨肌肉表现出缺陷的基础和胰岛素刺激受体激活.
- 一个关键的胰岛素信号蛋白Akt2显示辐射诱导的硫化,表明失调.
- 蛋白质组学揭示了辐射肌肉中的线粒体和过氧体相关蛋白质的上调调节.
- 线粒体裂变和融合的标记增加表明线粒体周转率和动态发生了变化.
结论:
- 被辐射的骨肌肉表现出持续的胰岛素抵抗.
- 辐射暴露导致细胞内蛋白质氧化,并改变肌肉中的线粒体功能.
- 骨肌肉中的这些分子和功能变化有助于辐射诱导的血糖失调和糖尿病.
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