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Published on: November 16, 2011
高血糖激活的11β-hydroxysteroid脱酶1型增加了内分泌网膜应激和皮肤屏障功能障碍
Young Bin Lee1, Hyun Jee Hwang1, Eunjung Kim1
1Department of Dermatology, Yonsei University Wonju College of Medicine, 20 Ilsan-ro, Wonju, 26426, Republic of Korea.
糖尿病 (DM) 皮肤问题源于高血糖,激活皮肤11β-基固醇脱酶1型 (11β-HSD1),增加活性葡萄皮质类药物,ER压力和屏障缺陷.
科学领域:
- 内分泌学 在内分泌学.
- 皮肤病学 皮肤病学
- 代谢障碍 代谢障碍 代谢障碍
背景情况:
- 糖尿病 (DM) 与皮肤屏障功能障碍和脂质异常有关.
- 这些皮肤变化类似于葡萄糖皮质激素过量和老化皮肤所见的变化.
- 葡萄糖皮质体 (GC) 活性由11β-基固醇脱酶1型 (11β-HSD1) 调节,该酶将非活性转化为活性GC.
研究的目的:
- 调查DM中高血糖会影响全身GC恒温的假设.
- 确定皮肤11β-HSD1和GC的作用是否有助于DM的内分泌网膜 (ER) 应激和屏障缺陷.
- 为了比较11β-HSD1,活性GC和ER压力在高血糖和正常血糖条件下.
主要方法:
- 在高血糖和正常血糖条件下培养出正常的人类角质细胞.
- 在细胞培养中利用了11β-HSD1siRNA和ER压力抑制剂.
- 在不同年龄的db/db小鼠中检查了11β-HSD1,活性GC和ER压力标志物.
- 在db/db小鼠中使用局部11β-HSD1抑制剂.
主要成果:
- 过高血糖症随着时间的推移增加了质细胞中的11β-HSD1和皮质醇水平.
- 在高血糖症下,11β-HSD1倒退可以防止皮质醇升高.
- 经过ER应激抑制,减少了11β-HSD1和皮质醇的产生.
- 较老的db/db小鼠表现出较高的角质层 (SC) 皮质和皮肤11β-HSD1水平.
- 在db/db小鼠的局部11β-HSD1抑制降低了SC皮质和改善了皮肤屏障功能.
结论:
- 在DM中高血糖可能会破坏系统性GC平衡.
- 通过高血糖症激活皮肤11β-HSD1可以导致局部GC过量.
- 这种局部GC过量导致糖尿病患者的ER压力增加和皮肤屏障功能受损.
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