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优血糖受压力防御因子肝细胞NRF1的影响,而不是NRF2的影响
May G Akl1, Raquel Baccetto2, Brynne M Stebbings2
1Department of Anatomy, Physiology, and Pharmacology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada; Department of Physiology, Faculty of Medicine, University of Alexandria, Alexandria, Egypt.
Biochemical and biophysical research communications
|May 28, 2023
概括
肝细胞核因子红色素2相关因子-1 (NRF1) 缺乏会降低血糖,这表明它在葡萄糖稳定中起着作用. NRF1,而不是NRF2,影响肝脏糖原和生长激素/IGF-1轴.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 内分泌学 在内分泌学.
- 代谢调节 代谢调节 代谢调节
背景情况:
- 肝细胞的压力信号破坏葡萄糖代谢和全身葡萄糖平衡.
- 压力防御机制在控制葡萄糖平衡中的作用尚不清楚.
- 核因素红色素2相关因子-1 (NRF1) 和-2 (NRF2) 是肝细胞中应激防御的关键转录因子.
研究的目的:
- 确定肝细胞中NRF1和NRF2在葡萄糖平衡中独立且互补的作用.
- 研究肝细胞特异性NRF1和/或NRF2丧失对血糖的影响.
主要方法:
- 在小鼠中,成年开始的,肝细胞特异的NRF1,NRF2或两者都被删除.
- 给小鼠吃了一种轻度压力饮食 (脂肪,果糖,胆固醇) 1-3周.
- 分析血糖,肝脏糖原,糖原合成酶表达和循环激素 (生长激素,IGF-1).
主要成果:
- NRF1缺乏和NRF1/NRF2缺乏导致血糖降低,有时导致低血糖.
- 单独NRF2缺乏并没有影响血糖.
- 在瘦素缺乏肥胖/糖尿病小鼠中,NRF1缺乏的降低血糖缺乏,这表明NRF1可以抵消低血糖症.
- NRF1 缺乏与肝脏糖原减少,糖原合成酶表达减少以及生长激素/IGF-1 水平变化相关.
结论:
- 肝细胞NRF1在调节葡萄糖平衡中起着重要作用.
- NRF1对葡萄糖平衡的影响可能涉及肝脏糖原储存和生长激素/IGF-1轴的调节.
- NRF1,但不是NRF2,在特定的饮食压力条件下维持葡萄糖平衡似乎至关重要.
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