循环赫西米德对翻译的短期抑制同时影响雌性小鼠小岛上的线粒体功能和胰岛素分泌
Mohammed Alshafei1, Torben Schulze1, Mai Morsi1,2
1Institute of Pharmacology, Toxicology and Clinical Pharmacy, Technische Universität Braunschweig, D38106 Braunschweig, Germany.
International journal of molecular sciences
|October 28, 2023
概括
循环赫西米德 (CHX) 通过影响线粒体功能和蛋白质合成,损害了新鲜岛屿中葡萄糖刺激的胰岛素释放. 这种效应在培养的小岛上有所不同,这表明在β细胞中具有不同的线粒体作用.
科学领域:
- 内分泌学 在内分泌学.
- 细胞生物学 细胞生物学
- 代谢过程中的代谢.
背景情况:
- 葡萄糖刺激胰岛素释放和胰腺β细胞中的蛋白质生物合成.
- 这两个过程之间的相互作用,特别是关于线粒体信号的相互作用,仍然不完全理解.
研究的目的:
- 为了研究蛋白质生物合成和葡萄糖刺激的胰岛素分泌之间的相互作用.
- 探索循环赫西米德 (CHX) 在调节β细胞功能和线粒体活动中的作用.
主要方法:
- 使用了外围使用的,新鲜分离的和培养的NMRI小鼠岛.
- 在葡萄糖或托尔布塔米德刺激之前,使用10μM循环赫西米德 (CHX) 抑制蛋白质生物合成.
- 测量胰岛素释放,细胞内 ([Ca2+]i),氧消耗率 (OCR) 和NAD (P) H/FAD自光.
主要成果:
- 在新鲜小岛上,CHX减少了葡萄糖和托尔胺刺激的胰岛素释放,但在培养小岛上没有.
- CHX降低了亲胰岛素含量,并在新鲜和培养岛屿中适度减少了[Ca2+]i的增加.
- 在新鲜的小岛上,CHX使葡萄糖诱导的OCR和自光变化变得淡,表明线粒体干扰.
结论:
- 短期CHX暴露会干扰β细胞中的线粒体信号传递.
- 线粒体功能和对CHX的反应在新鲜和培养岛屿之间有所不同.
- CHX的作用可能来自于线粒体蛋白质的抑制合成,而不是非目标效应.
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