ангиотензин-(1-7) 通过激活PI3K/Akt/FoxO1通路来改善岛屿β细胞分离
Hao Guo1, Dandan Guo2, Min An1
1Department of Endocrinology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
Protein and peptide letters
|November 13, 2023
概括
ангиотензин-(1-7) [Ang-(1-7) ]通过激活PI3K/Akt/FoxO1通路,防止高葡萄糖诱导的胰腺小岛β细胞脱差. 这改善了胰岛素分泌,并恢复了β细胞特异性基因表达.
科学领域:
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 岛屿β细胞脱差是减少胰岛素分泌的主要原因.
- ангиотензин-(1-7) [Ang-(1-7) ]显示出减轻高葡萄糖诱导的β细胞亡和脱差的潜力.
- 涉及到的精确信号通路仍然不清楚.
研究的目的:
- 研究Ang-(1-7) 对高葡萄糖诱导的小岛β细胞脱差的保护作用.
- 阐明酸丁醇-3-激酶/蛋白激酶B/叉头盒转录因子O1 (PI3K/Akt/FoxO1) 信号通路在这个过程中的作用.
主要方法:
- 利用MIN6小鼠岛屿β细胞系暴露在高葡萄糖条件下.
- 使用Ang-(1-7) 配合或不配合MasR抗体 (A-779) 或PI3K抑制剂 (LY294002).
- 评估了葡萄糖刺激胰岛素分泌 (GSIS),β细胞特异因子 (Pdx1,MafA),原始细胞标记物 (Oct4,Nanog) 和PI3K/Akt/FoxO1通路激活 (西斑,RT-PCR).
主要成果:
- 高葡萄糖诱导β细胞脱差,降低胰岛素分泌和Pdx1/MafA表达,同时增加Oct4/Nanog.
- Ang-(1-7) 的干预逆转了这些影响,增加了胰岛素分泌和Pdx1/MafA,并减少了Oct4/Nanog.
- Ang-(1-7) 的作用被A-779和LY294002阻断,这表明MasR和PI3K/Akt/FoxO1通路的参与.
结论:
- ангиотензин-(1-7) [Ang-(1-7) ]有效地防止高葡萄糖诱导的胰腺β细胞分化.
- 激活PI3K/Akt/FoxO1信号通路是Ang-(1-7) 保护作用的关键机制.
- 这项研究为Ang-(1-7) 对糖尿病治疗的治疗潜力提供了新的见解.
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