肝脏胰岛素化作为甘油三酸代谢失调的驱动因素
Joshua R Cook1, Meredith A Hawkins2, Utpal B Pajvani3
1Naomi Berrie Diabetes Center, Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, Columbia University College of Physicians & Surgeons, New York City, NY, USA. jrc2175@cumc.columbia.edu.
Nature metabolism
|July 17, 2023
概括
与代谢功能障碍相关的脂肪肝疾病 (MAFLD) 与胰岛素抵抗有关. 即使是轻微的胰岛素升高也会导致肝脏中的脂肪积累,原因是选择性胰岛素抵抗.
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.
- 代谢疾病 代谢疾病
背景情况:
- 与代谢功能障碍相关的脂肪肝疾病 (MAFLD) 非常普遍,并与胰岛素抵抗和2型糖尿病有关.
- 关联MAFLD和胰岛素作用受损的确切机制尚未完全理解.
- 胰岛素抵抗是代谢综合征的标志,影响葡萄糖和脂质代谢.
研究的目的:
- 审查人类数据并阐明胰岛素在MAFLD中的病因作用.
- 在MAFLD中研究胰岛素刺激甘油三生物合成的选择性保存.
- 在MAFLD和高胰岛素血症的背景下解释"选择性胰岛素抵抗"现象.
主要方法:
- 审查现有的人类数据和临床研究.
- 分析肝细胞中的胰岛素信号通路.
- 专注于胰岛素对肝脏葡萄糖生产和甘油三生物合成的差异调节.
主要成果:
- 胰岛素抑制肝脏葡萄糖 (HGP) 生产的能力在胰岛素耐药性方面受到损害.
- 胰岛素对肝脏甘油三酸 (TG) 生物合成的刺激相对保持.
- 对于TG积累的肝细胞过程可能比调节HGP的过程需要更少的胰岛素信号 ("胰岛素化").
结论:
- 胰岛素耐药性状态下的高胰岛素血症可能足够维持肝脏TG生物合成.
- 持续的,即使是适度的,在亲脂生环境中胰岛素的升高可能会导致肝脏显著的TG积累.
- 这种选择性胰岛素耐药性有助于MAFLD在具有代谢障碍的个体的发病.
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