MFGE8 通过 PTP1BB 抑制胰岛素信号传递
Ritwik Datta1, Michael J Podolsky1, Christopher D Yang1
1Cardiovascular Research Institute, University of California, San Francisco, CA 94158.
bioRxiv : the preprint server for biology
|July 3, 2023
概括
结合整合素αvβ5的乳脂球体表皮生长因子8 (MFGE8) 通过控制胰岛素受体β (IRβ) 通过PTP1B去化,调节胰岛素信号传递. 这会影响葡萄糖的吸收,并与人类的胰岛素抵抗有关.
科学领域:
- 细胞生物学 细胞生物学
- 代谢信号传递是代谢信号传递.
- 整体的功能是整体的.
背景情况:
- 整合素调解细胞矩阵相互作用,影响细胞信号通路.
- 与αvβ5整合素结合的乳脂球体表皮生长因子8 (MFGE8) 与胰岛素信号终止有关.
- 在胰岛素受体 (IR) 信号传递中β5整合素作用的精确机制需要进一步阐明.
研究的目的:
- 研究β5整合素与胰岛素受体β子单元 (IRβ) 之间的相互作用如何影响IRβ酸化的机制.
- 确定蛋白氨酸酸酶1B (PTP1B) 在调解MFGE8和β5对胰岛素信号传递的影响中的作用.
- 在人类队列中探索血清MFGE8水平和胰岛素抵抗之间的相关性.
主要方法:
- 研究骨肌肉中β5整蛋白与IRβ的结合.
- 评估β5封锁和MFGE8对与IRβ结合的PTP1B的影响.
- 测量肌管和野生类型与PTP1B淘汰小鼠的胰岛素刺激葡萄糖吸收.
- 在人类队列中分析血清MFGE8水平,并将其与胰岛素抵抗指数相关联.
主要成果:
- MFGE8促进,而β5阻断,PTP1B与IRβ结合,影响IRβ脱.
- MFGE8将β5-PTP1B复合物招募到IRβ,从而终止了正规的胰岛素信号传递.
- 在野生型小鼠中,β5阻塞增强了胰岛素刺激的葡萄糖吸收,但在PTP1B淘汰小鼠中并非如此.
- 血清MFGE8水平与人类的胰岛素抵抗标志物有积极的相关性.
结论:
- 与αvβ5整合素结合的MFGE8通过招募PTP1B去化IRβ来终止胰岛素信号传递.
- 在调节胰岛素受体信号传递方面,PTP1B作用于MFGE8的下游.
- MFGE8及其与β5整合素的相互作用代表了胰岛素耐药性和2型糖尿病的潜在治疗标.
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