Background

The mechanochemical enzyme dynamin mediates endocytosis and regulates neuroendocrine cell exocytosis. Enteroendocrine L cells co-secrete the anorectic gut hormones glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) postprandially and is a potential therapeutic target for metabolic diseases. In the present study, we aimed to determine if dynamin is implicated in human L cell secretion.

Methods

Western blot was performed on the murine L cell line GLUTag. Static incubation of human colonic mucosae with activators and inhibitors of dynamin was carried out. GLP-1 and PYY contents of the secretion supernatants were assayed using ELISA.

Results and conclusion

s: Both dynamin I and II are expressed in GLUTag cells. The dynamin activator Ryngo 1–23 evoked significant GLP-1 and PYY release from human colonic mucosae while the dynamin inhibitor Dynole 3–42 significantly inhibited release triggered by known L cell secretagogues. Thus, the cell signaling regulator dynamin is able to bi-directionally regulate L cell hormone secretion in the human gut and may represent a novel target for gastrointestinal-targeted metabolic drug development.

中文翻译：

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Dynamin 调节人肠道中 L 细胞的分泌

背景

机械化学酶 dynamin 介导内吞作用并调节神经内分泌细胞胞吐作用。肠内分泌 L 细胞在餐后共同分泌厌食肠道激素胰高血糖素样肽 1 (GLP-1) 和肽 YY (PYY)，是代谢疾病的潜在治疗靶点。在本研究中，我们旨在确定动力蛋白是否与人类 L 细胞分泌有关。

方法

对鼠 L 细胞系 GLUTag 进行蛋白质印迹。进行人结肠粘膜与动力蛋白激活剂和抑制剂的静态温育。使用ELISA测定分泌上清液的GLP-1和PYY含量。

结果和结论

s: dynamin I 和 II 都在 GLUTag 细胞中表达。dynamin 激活剂 Ryngo 1-23 引起人结肠粘膜显着 GLP-1 和 PYY 释放，而 dynamin 抑制剂 Dynole 3-42 显着抑制已知 L 细胞促分泌素触发的释放。因此，细胞信号调节剂 dynamin 能够双向调节人体肠道中的 L 细胞激素分泌，并可能代表胃肠道靶向代谢药物开发的新靶点。