化PKM2调节糖尿病中的内皮依赖血管扩张
1Vascular Disease and Transformation Medical Center, Third Xiangya Hospital, Central South University, Changsha 410013. 18826401647@163.com.
化酸激酶M2 (p-PKM2) 通过损害血管功能,有助于糖尿病大血管病. 用TEPP-46抑制p-PKM2改善了糖尿病小鼠和细胞的血管扩张和氧化水平.
科学领域:
- 生物化学和分子生物学
- 内分泌学和新陈代谢学
- 心血管研究研究心血管研究
背景情况:
- 内皮依赖血管扩张功能障碍是糖尿病大血管病的关键因素.
- 高水平的葡萄糖会破坏内皮细胞的功能,影响糖解和能量产生.
- 类型M2的Pyruvate kinase异酶 (PKM2) 是糖解中的关键酶;它的酸化 (p-PKM2) 降低了活性并影响了葡萄糖代谢.
研究的目的:
- 研究酸化PKM2 (p-PKM2) 在高葡萄糖诱导的内皮功能障碍中的作用.
- 探索p-PKM2影响糖尿病宏血管病的内皮依赖血管扩张的机制.
- 使用TEPP-46.6评估抑制PKM2酸化的治疗潜力.
主要方法:
- 糖尿病 (db/db) 和野生型 (WT) 的小鼠被TEPP-46或载体控制器治疗了12周.
- 胸前动脉和血分析了p-PKM2,PKM2和氧化 (NO) 水平,并评估了血管扩张功能.
- 人类静脉内皮细胞 (HUVECs) 被暴露在高葡萄糖中,有或没有TEPP-46,以测量NO生产和PKM2/eNOS酸化.
主要成果:
- 糖尿病小鼠表现出增加的p-PKM2和受损的内皮依赖血管扩张,NO水平降低.
- 在糖尿病小鼠中,TEPP-46治疗降低了p-PKM2,改善了血管扩张,并增加了血NO水平.
- 高葡萄糖增加了p-PKM2并减少了HUVEC中的NO;TEPP-46逆转了这些影响并减少了p-eNOS (ser1177).
结论:
- 升高的p-PKM2与高葡萄糖诱导的内皮功能障碍和糖尿病大血管病症有关.
- 通过TEPP-46抑制p-PKM2,通过潜在地恢复p-eNOS (ser1177) /NO通路来改善内皮功能障碍.
- 向PKM2酸化是糖尿病大血管病的潜在治疗策略.
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