Zhang Mengren, Shi Xiaoxia, Luo Mengxin, Lan Qi, Ullah Hayan, Zhang Cong, Li Shuangyue, Chen Xiaochi, Wang Yachen, Piao Fengyuan
Department of Occupational and Environmental Health, Dalian Medical University, Dalian, 116044, China.
Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian, 116044, Liaoning, China.
Amino Acids. 2021 Mar;53(3):395-406. doi: 10.1007/s00726-021-02957-1. Epub 2021 Feb 18.
Diabetic peripheral neuropathy (DPN) is a common complication of diabetes and axonopathy is its main pathological feature. Previous studies suggested an advantage of taurine against diabetes. However, there are few reports which study the effect of taurine against axonopathy. In this study, we confirmed that taurine significantly decreased blood glucose level, mitigated insulin resistance and improved dysfunctional nerve conduction in diabetic rats. Taurine corrected damaged axonal morphology of sciatic nerve in diabetic rats and induced axon outgrowth of Dorsal root ganglion (DRG) neurons exposed to high glucose. Taurine up-regulated phosphorylation levels of PI3K, Akt, and mTOR in sciatic nerve of diabetic rats and DRG neurons exposed to high glucose. However, Akt and mTOR inhibitors (MK-2206 and Rapamycin) blocked the effect of taurine on improving axonal damage. These results indicate that taurine ameliorates axonal damage in sciatic nerve of diabetic rats by activating PI3K/Akt/mTOR signal pathway. Our findings provide taurine as a potential candidate for axonopathy and a new evidence for elucidating protective mechanism of taurine on DPN.
糖尿病周围神经病变（DPN）是糖尿病常见的并发症，轴突病变是其主要病理特征。既往研究提示牛磺酸对糖尿病具有益处。然而，很少有报告研究牛磺酸对轴突病变的影响。在本研究中，我们证实牛磺酸可显著降低糖尿病大鼠的血糖水平，减轻胰岛素抵抗，并改善神经传导功能障碍。牛磺酸纠正了糖尿病大鼠坐骨神经受损的轴突形态，并诱导了暴露于高糖环境的背根神经节（DRG）神经元的轴突生长。牛磺酸上调了糖尿病大鼠坐骨神经和暴露于高糖环境的DRG神经元中PI3K、Akt和mTOR的磷酸化水平。然而，Akt和mTOR抑制剂（MK-2206和雷帕霉素）阻断了牛磺酸改善轴突损伤的作用。这些结果表明，牛磺酸通过激活PI3K/Akt/mTOR信号通路改善糖尿病大鼠坐骨神经的轴突损伤。我们的研究结果为轴突病变提供了牛磺酸这一潜在候选物，并为阐明牛磺酸对DPN的保护机制提供了新的证据。
