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分泌的EMC10抑制了小鼠的肌肉GLUT4活性和葡萄糖吸收

Shuoshuo Jin¹, Wei Wu¹, Shan Liu¹

¹Department of Endocrinology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.

The Journal of biological chemistry

|May 29, 2025

概括

分泌的细胞内网膜蛋白质复合体子单元10 (scEMC10) 阻碍了肌肉的葡萄糖吸收,并恶化了葡萄糖不耐受. 抑制scEMC10可以改善葡萄糖平衡,这表明它是2型糖尿病的治疗点.

科学领域:

生物化学生物化学
代谢研究研究代谢研究
分子生物学分子生物学

背景情况:

肌肉的葡萄糖吸收对于葡萄糖平衡至关重要.
内质网膜蛋白复合体子单元10 (scEMC10) 的分泌异型与葡萄糖耐受性,胰岛素耐药性和高血糖相关.
scEMC10在调节肌肉葡萄糖代谢中的确切作用尚不清楚.

研究的目的:

调查scEMC10在调节肌肉葡萄糖摄取中的作用及其对葡萄糖平衡的影响.
阐明scEMC10影响肌肉葡萄糖代谢的分子机制.
评估抑制scEMC10的治疗潜力,以控制2型糖尿病.

主要方法:

使用Emc10基因淘汰 (KO) 的小鼠模型,并用重组scEMC10.10治疗.
评估了小鼠模型和肌细胞体中的葡萄糖摄取,GLUT4表达和细胞内葡萄糖代谢.
研究了scEMC10对AMP激活蛋白激酶 (AMPK) 和胰岛素信号通路的影响.
在小鼠中用中和抗体对抗scEMC10,以评估治疗疗效.

主要成果:

Emc10基因KO增加了肌肉的葡萄糖吸收,而scEMC10治疗减少了它,以及GLUT4表达.
scEMC10抑制了肌细胞中的GLUT4表达和膜转位,降低了参与细胞内葡萄糖代谢的基因.
scEMC10抑制了AMPK激活和肌肉中的胰岛素信号级联.
使用中和抗体抑制scEMC10,增强了肌肉葡萄糖吸收,GLUT4表达和膜转位,从而改善了全身葡萄糖平衡.

结论:

scEMC10作为肌肉葡萄糖吸收的新型抑制剂.
scEMC10通过干扰肌肉葡萄糖代谢和信号通路,对葡萄糖平衡产生负面影响.
抑制scEMC10为2型糖尿病治疗提供了一个有前途的治疗策略.

关键词:

在GLUT4中使用GLUT4.摄取葡萄糖的时间泄露的EMC1010可以被分泌.这是骨肌肉的骨架肌肉.

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