摘要
目的探讨吐根碱通过胰高血糖素样肽-1受体(glucagon-like peptide-1 receptor,GLP-1R)促进离体大鼠胰岛组织胰岛素分泌作用。方法分离大鼠胰岛组织进行胰岛素分泌实验,根据实验设计使用不同浓度的吐根碱(2、10、50μmol·L^(-1))、不同浓度葡萄糖(2.8、11.1、16.7 mmol·L^(-1))以及特异性GLP-1R拮抗剂Exendin(9-39)孵育胰岛组织。酶联放射免疫的检测方法测定每组上清液胰岛素分泌量。使用SYBYL-X2.0软件将小分子化合物与GLP-1R(PDB代码:5NX2)进行对接。结果胰岛素分泌实验结果显示在高糖(11.1 mmol·L^(-1))条件下,胰岛素分泌量在吐根碱作用下明显升高,且具有剂量依赖性。低糖(2.8 mmol·L^(-1))条件下,胰岛素分泌量在吐根碱干预下没有明显变化,但在高糖(11.1、16.7 mmol·L^(-1))条件下,胰岛素分泌量在吐根碱作用下明显升高,具有类似GLP-1R激动剂葡萄糖浓度依赖性促胰岛素分泌特点。吐根碱与GLP-1R对接打分是Total Score=6.82,C Score=5,表明吐根碱与GLP-1R有良好的亲和力。当GLP-1R被Exendin(9-39)阻断后,吐根碱促胰岛素分泌作用明显降低。结论吐根碱通过激活GLP-1R发挥促离体大鼠胰岛组织胰岛素分泌作用。
Aim To study the effect of emetine on insulin secretion through glucagon-like peptide-1 receptor(GLP-1R).Methods Isolating rat islets were used to carry out insulin secretion experiment.Islets were incubated with different concentrations of emetine(2,10,50μmol·L^(-1)),different concentrations of glucose solution(2.8,11.1,16.7 mmol·L^(-1))or specific GLP-1R antagonist Exendin(9-39).The amount of insulin secretion in the supernatant of each group was determined by an enzyme-linked radioimmunoassay.Small molecule compounds were docked to GLP-1R(PDB code:5NX2)using SYBYL-X2.0 software.Results Emetine could promote insulin secretion in high glucose(11.1mmol·L^(-1))in a dose-dependent manner.In low glucose(2.8 mmol·L^(-1)),insulin secretion did not change after intervention of emetine.But in high glucose(11.1,16.7 mmol·L^(-1)),insulin secretion significantly increased under the treatment of emetine in a glucose-dependent manner.The docking score of emetine and GLP-1R was Total Score=6.82,C Score=5,indicating that emetine had a good binding affinity with GLP-1R.Using Exendin(9-39)to block GLP-1R,the insulinotropic effect of emetine was reduced.Conclusion Emetine could promote insulin secretion,which is related to the activation of GLP-1R.
作者
薛欢
路志红
王彬
余思婷
张茜
胡斌
曾庆轩
章毅
XUE Huan;LU Zhi-hong;WANG Bin;YU Si-ting;ZHANG Xi;HU Bin;ZENG Qing-xuan;ZHANG Yi(Dept of Pharmacology,Ministry of Education,Shanxi Medical University,Taiyuan 030001,China;School of Pharmacy,Ministry of Education,Shanxi Medical University,Taiyuan 030001,China;Medicinal Basic Research Innovation Center of Chronic Kidney Disease,Ministry of Education,Shanxi Medical University,Taiyuan 030001,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2024年第7期1267-1272,共6页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No 81973378,82073909)
中央引导地方科技发展资金项目(No YDZJSX2022A059)
山西省专利转化专项计划(No 202304016)
山西省“四个一批”科技兴医创新计划项目(No 2023XM022)
山西省青年科学研究项目(No 202103021223219)。
关键词
胰高血糖素样肽-1受体
分子对接
2型糖尿病
吐根碱
胰岛素分泌
小分子化合物
glucagon-like peptide-1 receptor
molecular docking
type 2 diabetes mellitus
emetine
insulin secretion
small molecular compound