脂质诱导的胰岛素抵抗:解开机制
Varman T Samuel1, Kitt Falk Petersen, Gerald I Shulman
1Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06536-8012, USA.
Lancet (London, England)
|July 9, 2010
概括
脂质通过破坏肌肉和肝脏中的葡萄糖运输来降低胰岛素敏感性,这是肥胖和2型糖尿病的关键机制. 这通过二甲基甘油积累激活蛋白激酶C来发生,从而影响胰岛素信号传递.
科学领域:
- 生物化学 生物化学
- 代谢性疾病是一种代谢性疾病.
- 蜂信号传输是如何进行的
背景情况:
- 胰岛素抵抗与肥胖有关,早期理论表明脂质抑制糖解.
- 最近的研究强调,胰岛素刺激的葡萄糖运输缺陷是骨肌肉的主要原因.
研究的目的:
- 阐明骨肌肉和肝脏中脂质诱导的胰岛素抵抗机制.
- 提出一种统一的假设,针对各种疾病的胰岛素抵抗.
主要方法:
- 审查关于脂质代谢和胰岛素信号传递的现有文献.
- 细胞内脂质积累的分析,特别是二甲基甘油.
- 针对脂质的反应中蛋白激酶C激活的研究.
主要成果:
- 在肌肉和肝脏中积累的脂质,特别是二甲基甘油,会损害胰岛素的信号传递.
- 这种损伤源于胰岛素刺激的葡萄糖运输缺陷,而不是糖解抑制.
- 由二甲糖醇激活新型蛋白激酶C是一种关键途径.
结论:
- 细胞内二甲基甘油积累和随后的蛋白激酶C激活解释了脂质诱导的胰岛素耐药性.
- 这种机制与肥胖,2型糖尿病,脂质缩和衰老有关.
- 它还解释了 thiazolidinediones 的胰岛素敏感作用.
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