葡萄糖通过INSP3R1介导的肝脂解刺激葡萄糖生成
Rachel J Perry1,2, Dongyan Zhang1, Mateus T Guerra1
1Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.
Nature
|March 6, 2020
概括
葡萄糖通过INSP3R1刺激肝脏的脂肪燃烧和葡萄糖的产生. 向该受体可以逆转脂肪肝和2型糖尿病.
科学领域:
- 代谢疾病
- 肝病学
- 内分泌学
背景情况:
- 降低胰岛素/ 葡萄糖比例会影响2型糖尿病的肝糖代谢.
- 葡萄糖对肝脏葡萄糖的产生和线粒体氧化的作用机制尚不清楚.
研究的目的:
- 阐明葡萄糖对肝脏葡萄糖的产生和线粒体氧化的机制.
- 研究伊诺西三酸盐受体1 (INSP3R1) 在调解葡萄糖对肝脏的影响中的作用.
- 评估针对非酒精性脂肪肝和2型糖尿病的INSP3R1治疗潜力.
主要方法:
- 在动物中研究了葡萄糖对肝脂肪三糖 lipase 活性,肝内 lipolysis,乙-CoA 含量和 pyruvate carboxylase 流量的影响.
- 检查了对葡萄糖的反应中的线粒体脂肪氧化.
- 使用INSP3R1 (Itpr1) 敲除小鼠来评估INSP3R1在调解葡萄糖的作用中的必要性.
- 对饮食诱导的肥胖小鼠和老鼠进行慢性葡萄糖治疗.
主要成果:
- 葡萄糖通过激活INSP3R1刺激肝脏葡萄糖生成和线粒体脂肪氧化.
- 在动物中,慢性葡萄糖治疗逆转了饮食引起的肝硬化和胰岛素耐药性.
- 这些有益效应在INSP3R1淘汰小鼠中被取消,证实了受体的关键作用.
结论:
- 通过INSP3R1传递葡萄糖信号,增强肝脏脂肪的氧化和葡萄糖生成.
- 通过葡萄糖激活INSP3R1可以逆转肝脂症并改善葡萄糖不耐受性.
- 在非酒精性脂肪肝和2型糖尿病中,INSP3R1成为潜在的治疗点.
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