对葡萄糖敏感的myokine/ cardiokine MG53调节全身胰岛素反应和代谢平衡
Hong-Kun Wu1, Yan Zhang1, Chun-Mei Cao1
1State Key Laboratory of Membrane Biology, Institute of Molecular Medicine (H.-K.W., Y.Z., C.-M.C., X.H., M.F., Y.Y., L.J., G.C., P.J., S.Z., R.S., W.P., F.L., J.G., L.T., Y.H., D.S., Z.Z., F.L., R.-P.X.).
Circulation
|December 28, 2018
概括
三素53 (MG53) 通过肌肉和心脏分泌,以应对高血糖,导致胰岛素抵抗. 中和MG53为2型糖尿病 (T2DM) 提供了潜在的治疗方法.
科学领域:
- 内分泌学
- 代谢综合征研究
- 肌肉生理学
背景情况:
- 肌肉特异性E3联酶Mitsugumin 53 (MG53) 降解胰岛素受体,导致胰岛素抵抗,代谢综合征和2型糖尿病 (T2DM).
- MG53在调节胰岛素敏感性和能量代谢中的系统作用尚不清楚,尽管有肌肉分泌的肌肉激素影响系统过程的证据.
研究的目的:
- 调查MG53是否作为调节全身胰岛素敏感性和代谢平衡的肌肉蛋白/心脏蛋白.
- 探索针对循环MG53作为T2DM治疗策略的潜力.
主要方法:
- 在高葡萄糖/胰岛素条件下,从动物心脏/骨肌中评估MG53蛋白度.
- 在有/没有T2DM的动物和人类中测量血清MG53水平.
- 在小鼠模型中评估了全身MG53输送和抗体中和的影响.
- 分析了MG53与胰岛素受体细胞外域的相互作用.
主要成果:
- 高葡萄糖/胰岛素刺激心脏和骨肌肉的MG53分泌.
- 在糖尿病患者和动物中,MG53的循环水平较高.
- 系统性MG53输送诱导胰岛素抵抗和代谢综合征;MG53中和显示T2DM小鼠的治疗效果.
- MG53与胰岛素受体外细胞域结合,作为一种全质阻断剂.
结论:
- 通过抑制胰岛素信号,MG53作为一种对葡萄糖敏感的肌动素/心动素,加剧胰岛素耐药性.
- 针对循环中的MG53为T2DM及其并发症提供了一种新的治疗方法.
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