实时检测从单个岛屿释放的体静止素,发现2型糖尿病的高分泌
Mingyu Yang1, Kousik Mandal1, Moa Södergren1
1Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
Acta physiologica (Oxford, England)
|January 13, 2025
概括
2型糖尿病与胰腺三角细胞的体静止素分泌量增加有关. 一种新的记者测定能够实时检测体静止素释放,有助于研究岛屿功能和功能障碍.
科学领域:
- 内分泌学 在内分泌学.
- 细胞生物学 细胞生物学
- 糖尿病研究 糖尿病研究
背景情况:
- 胰腺的三角细胞分泌索马托斯塔丁,它是胰岛素和葡萄糖的近调节剂.
- 索马托斯坦素释放的动力学及其在糖尿病中的变化仍然不清楚.
- 了解体静止素分泌对于理解小岛的功能和功能障碍至关重要.
研究的目的:
- 开发一种实时检测从单个胰腺小岛释放的体静止素的工具.
- 为了研究 somatostatin 的释放动力学.
- 为了确定体静止素分泌是否在2型糖尿病中发生变化.
主要方法:
- 通过在HeLa细胞中共同表达体静止素受体SSTR2,Gα15和光Ca2+传感器来生成记者细胞.
- 利用记者细胞检测体静止素诱导的细胞质Ca2+度 ([Ca2+]i) 变化.
- 在各种刺激条件下 (例如高葡萄糖,K+脱极化) 将报告测试应用于小鼠和人类小岛,包括来自2型糖尿病捐赠者的小岛.
主要成果:
- 在记者细胞中,索马托斯塔丁诱导的剂量依赖[Ca2+]i增加.
- 鼠标和人类小岛触发了记者细胞[Ca2+]i的升高,被SSTR2抗剂抑制.
- 与非糖尿病岛屿相比,来自2型糖尿病捐赠者的岛屿显示出较高的记者细胞[Ca2+]i反应,尽管发现的三角细胞较少.
结论:
- 2型糖尿病与人体静止素的过分分泌有关.
- 这种高分泌对胰岛素和葡萄糖分泌的副分泌调节有重大影响.
- 开发的记者细胞测定是未来对岛屿生理学和病理生理学中体静止素分泌的研究的一个有希望的工具.
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