线粒体二碳酸盐载体在体内中介于肝脏葡萄糖生成
Daniel J Pape1, Kelly C Falls-Hubert1, Ronald A Merrill1
1Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, Iowa City, IA 52240, USA.
bioRxiv : the preprint server for biology
|September 24, 2024
概括
线粒体二碳酸盐载体 (DiC) 出口碳用于肝脏葡萄糖生成 (GNG). 阻断DIC降低了葡萄糖的生产,并改善了2型糖尿病模型中的高血糖.
科学领域:
- 代谢过程中的代谢.
- 分子生物学分子生物学
- 内分泌学 在内分泌学.
背景情况:
- 肝脏葡萄糖生成 (GNG) 维持血糖,但在2型糖尿病 (T2D) 中病理上升.
- 乳酸盐和酸盐是进口到线粒体的关键GNG基质,但线粒体外GNG的出口机制尚不清楚.
研究的目的:
- 为了研究线粒体二碳酸盐载体 (DiC) 在肝 GNG 中的作用,使用乳酸/酸盐作为基质.
- 确定 DiC 是否调解 GNG 所需的碳出口,并有助于 T2D 病理生理学.
主要方法:
- 产生肝脏特异性DIC淘汰赛 (DiC LivKO) 的小鼠.
- 乳酸盐/酸盐耐受性测试,以评估葡萄糖代谢.
- 利用西方饮食 (WD) 养模式诱导肥胖和T2D类症状.
主要成果:
- 在乳酸/酸盐耐受性测试中,DiC LivKO小鼠表现出降低的血葡萄糖外流.
- 在DiC LivKO小鼠中,C-乳酸盐/-酸盐流入肝脏和血中的葡萄糖减少.
- 肥胖小鼠中的急性DiC缺失降低了乳酸/酸盐驱动的GNG,高血糖和高胰岛素血.
结论:
- 通过DiC导出线粒体碳对于从乳酸/酸盐的肝脏葡萄糖生成至关重要.
- DiC在T2D小鼠模型中观察到的葡萄糖平衡受损中发挥着重要作用.
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