肝脏酸合成调节肝脏和骨肌肉中的葡萄糖平衡
Jun Peng1, Liming Yu1, Linzhang Huang1
1Center for Pulmonary and Vascular Biology, Dept. of Pediatrics, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX, 75390, USA.
Molecular metabolism
|September 30, 2023
概括
肝脏的酸合成通过影响胰岛素和葡萄糖信号影响葡萄糖平衡. 减少化损害了肝脏葡萄糖的控制,但通过FGF21和肌肉葡萄糖吸收增强了全身胰岛素敏感性.
科学领域:
- 生物化学 生物化学
- 代谢研究研究 代谢研究
- 葡萄糖生物学 葡萄糖生物学
背景情况:
- 酸是一种葡萄糖衍生物,对糖蛋白和糖脂的功能至关重要.
- 酶UDP-GlcNAc 2-epimerase/ManNAc 激酶 (GNE) 调节了酸的合成.
- 肝酸在葡萄糖平衡中的作用在很大程度上仍未被探索.
研究的目的:
- 为了研究肝脏酸合成和化如何影响葡萄糖恒温.
- 阐明这些对肝脏和全身新陈代谢的影响背后的机制.
主要方法:
- 产生了一种肝细胞特异性GNE敲击小鼠模型.
- 评估系统性葡萄糖代谢,肝脏胰岛素和葡萄糖信号 in vivo 和初级肝细胞.
- 评估了外周胰岛素敏感性,并确定了潜在的分子机制.
主要成果:
- 肝脏GNE缺失导致肝脏葡萄糖生产的胰岛素抑制受损,这是由于降低了化和肝脏胰岛素受体降解的增加.
- 肝脏GNE缺陷使得葡萄糖受体功能减弱,降低其化和对葡萄糖的亲和力.
- 升级的肝FGF21增强了骨肌肉的葡萄糖处理,增加了整体葡萄糖耐受性和胰岛素敏感性.
结论:
- 肝脏酸合成和化是肝脏和外围组织中葡萄糖平衡的关键调节剂.
- 发现了一种新的代谢循环,其中葡萄糖衍生的甘氨酸会影响葡萄糖的全身控制.
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