Yun Ying, Guo Shimeng, Xie Xin
Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, China.
State Key Laboratory of Drug Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 189 Guo Shou Jing Road, Shanghai, 201203, China.
Cell Biosci. 2024 Aug 31;14(1):110. doi: 10.1186/s13578-024-01288-4.
Arginine vasopressin (AVP) has been reported to regulate insulin secretion and glucose homeostasis in the body. Previous study has shown that AVP and its receptor V1bR modulate insulin secretion via the hypothalamic-pituitary-adrenal axis. AVP has also been shown to enhance insulin secretion in islets, but the exact mechanism remains unclear.
In our study, we unexpectedly discovered that AVP could only stimulates insulin secretion from islets, but not β cells, and AVP-induced insulin secretion could be blocked by V1bR selective antagonist. Single-cell transcriptome analysis identified that V1bR is only expressed by the α cells. Further studies indicated that activation of the V1bR stimulates the α cells to secrete glucagon, which then promotes glucose-dependent insulin secretion from β cells in a paracrine way by activating GLP-1R but not GCGR on these cells.
Our study revealed a crosstalk between α and β cells initiated by AVP/V1bR and mediated by glucagon/GLP-1R, providing a mechanism to develop new glucose-controlling therapies targeting V1bR.
据报道，精氨酸加压素（AVP）可调节体内胰岛素分泌和葡萄糖稳态。先前的研究表明，AVP及其受体V1bR通过下丘脑-垂体-肾上腺轴调节胰岛素分泌。AVP还被证明可增强胰岛中的胰岛素分泌，但其确切机制仍不清楚。
在我们的研究中，我们意外地发现AVP只能刺激胰岛分泌胰岛素，而不能刺激β细胞，并且AVP诱导的胰岛素分泌可被V1bR选择性拮抗剂阻断。单细胞转录组分析确定V1bR仅由α细胞表达。进一步的研究表明，V1bR的激活刺激α细胞分泌胰高血糖素，然后通过激活这些细胞上的GLP-1R而非GCGR以旁分泌方式促进β细胞的葡萄糖依赖性胰岛素分泌。
我们的研究揭示了由AVP/V1bR引发并由胰高血糖素/GLP-1R介导的α细胞和β细胞之间的串扰，为开发针对V1bR的新型血糖控制疗法提供了一种机制。
