血造基衍生的甲基素-3 引起细胞和全身胰岛素耐药性
Pingping Li1, Shuainan Liu2, Min Lu3
1State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China; Diabetes Research Center of Chinese Academy of Medical Sciences, Beijing 100050, China; Division of Endocrinology and Metabolism, UC, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Cell
|November 5, 2016
概括
与肥胖相关的炎症涉及一种蛋白质 - - 加勒-3 (Gal3),该蛋白质会降低胰岛素的敏感性. 抑制Gal3可以改善肥胖小鼠的胰岛素敏感性,这表明它是胰岛素抵抗的治疗点.
科学领域:
- 免疫学
- 代谢疾病
- 分子生物学
背景情况:
- 肥胖导致胰岛素向组织的慢性炎症,导致胰岛素抵抗.
- 在肥胖患者中,甲素-3 (Gal3) 是巨细胞分泌的甲素,与胰岛素抵抗有关.
研究的目的:
- 研究加勒-3 (Gal3) 在肥胖引起的胰岛素抵抗中的作用.
- 探索Gal3与胰岛素受体 (IR) 和其信号通路的直接相互作用.
主要方法:
- 给小鼠使用Gal3诱导胰岛素耐药性和葡萄糖不耐受性.
- 在肥胖小鼠中基因和药理上抑制Gal3功能.
- 在体外研究Gal3对巨细胞的化学反应,肌细胞和脂肪细胞的葡萄糖摄取和肝细胞的葡萄糖输出.
- 评估Gal3与胰岛素受体 (IR) 的直接结合及其下游信号.
主要成果:
- 在小鼠中,Gal3引起胰岛素耐药性和葡萄糖不耐受性.
- 在肥胖小鼠中,Gal3抑制改善了胰岛素敏感性.
- 在实验室中,Gal3增强了巨细胞的迁移,减少了肌肉和脂肪细胞的葡萄糖吸收,并影响了肝脏的葡萄糖调节.
- Gal3直接与胰岛素受体 (IR) 结合,抑制其信号传递.
结论:
- 在肝细胞,脂肪细胞和肌细胞中介于胰岛素耐药性的关键作用.
- Gal3将炎症过程与胰岛素敏感性降低联系在一起.
- 抑制Gal3是治疗胰岛素耐药性和相关代谢障碍的潜在治疗策略.
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