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神经氨基酶抑制改善了糖尿病小鼠内皮功能
Christopher A Foote1,2, Francisco I Ramirez-Perez1, James A Smith1,3
1NextGen Precision Health, University of Missouri, Columbia, Missouri, United States.
American journal of physiology. Heart and circulatory physiology
|October 6, 2023
概括
在2型糖尿病 (T2D) 中神经氨基酶活性升高会通过降低葡萄糖来损害内皮功能. 抑制神经氨基酶可以恢复功能,但目前的扎纳米维尔剂量在人类中不足.
科学领域:
- 生物化学 生物化学
- 心血管生物学 心血管生物学
- 内分泌学 在内分泌学.
背景情况:
- 血神经氨基酶活性在2型糖尿病 (T2D) 中升高.
- 神经氨基酶从内皮糖结构中切割酸.
- 神经氨基酶的升高可能会导致T2D中的内皮功能障碍.
研究的目的:
- 调查循环神经氨基酶在T2D中内皮功能障碍中的作用.
- 评估神经氨基酶抑制作为T2D相关的内皮功能障碍的治疗策略的潜力.
主要方法:
- 在T2D受试者和对照者中测量了血神经aminidase活性,酸盐度和流媒体扩张 (FMD).
- 暴露的小鼠动脉和培养的内皮细胞对神经aminidase.
- 通过吸入给糖尿病小鼠和人类试验 (NCT04867707) 的神经氨基酶抑制剂扎纳米维尔.
主要成果:
- 与对照组相比,T2D受试者表现出较高的血神经aminidase活性,较低的酸盐,以及减少的口炎.
- 神经氨基酶暴露减少了小鼠动脉和内皮细胞中的口病和葡萄糖的存在.
- 赞纳米维尔在小鼠中改善了口病和葡萄糖,但由于血度不足,在人类中没有改善.
结论:
- 神经氨基酶是T2D中内皮功能障碍的关键调解者.
- 神经氨基酶抑制显示出治疗T2D内皮功能障碍的潜力.
- 目前的吸入性扎纳米维尔剂量不足以在人类中产生治疗效益.
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