一种GLP-1过表达肠类器官构建的方法

曾之扬, 陆佳微, 曹希雅, 王芯悦, 李大力

doi:10.16288/j.yczz.20-423

遗传 >

2021 , Vol. 43 >Issue 7: 694 - 703

DOI: https://doi.org/10.16288/j.yczz.20-423

技术与方法

一种GLP-1过表达肠类器官构建的方法

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1. 华东师范大学生命科学学院,上海市调控生物学重点实验室,上海 200241
2. 安徽理工大学医学院,淮南 232000
3. 上海交通大学附属第六人民医院南院消化内科,上海 201499

曾之扬,博士,博后,研究方向：发育生物学。E-mail: 52161300029@stu.ecnu.edu.cn

收稿日期: 2021-03-01

修回日期: 2021-04-14

网络出版日期: 2021-07-20

基金资助

国家重点研发计划编号(2019YFA0110802)

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A method for constructing GLP-1 overexpression intestinal organoids

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1. Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China
2. School of Medicine, Anhui University of Science and Technology, Huainan 232000, China
3. Department of Gastroenterology, South Campus of Sixth People's Hospital, Shanghai Jiaotong University, Shanghai 201499, China

Received date: 2021-03-01

Revised date: 2021-04-14

Online published: 2021-07-20

Supported by

Supported by the National Key R&D Program of China No(2019YFA0110802)

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摘要

胰高血糖素样肽1 (glucagon-like peptide 1, GLP-1)作为一种肠促胰岛素,主要由肠道L细胞分泌,由于其能够有效促进胰岛素的释放从而降低血糖,因此GLP-1及其类似物在2型糖尿病的治疗上具有良好的应用前景。本研究优化了慢病毒感染类器官的方法,利用该方法成功构建了GLP-1过表达的小鼠小肠类器官(organoids)。结果显示该类器官分泌的GLP-1能够有效地提高野生型及糖尿病小鼠的葡萄糖耐受能力。因此,本研究构建的GLP-1过表达类器官可以为2型糖尿病的治疗提供一种新的策略。

关键词： 胰高血糖素样肽1; 2型糖尿病; 小肠类器官

本文引用格式

曾之扬, 陆佳微, 曹希雅, 王芯悦, 李大力 . 一种GLP-1过表达肠类器官构建的方法[J]. 遗传, 2021 , 43(7) : 694 -703 . DOI: 10.16288/j.yczz.20-423

Abstract

As a potent insulinotrophic hormone, glucagon-like peptide 1 (GLP-1) is mainly secreted by intestinal L cells, which can effectively promote the release of insulin and thus reduce blood glucose. Therefore, GLP-1 and its analogs have a good prospect in the treatment of type 2 diabetes. In this study, we constructed mouse intestinal organoids that overexpress GLP-1 by optimizing the GLP-1 lentivirus infection method. We found that supernatants secreted by the GLP-1 overexpression organoids effectively enhanced glucose tolerance in wild-type and diabetic mouse. Thus, the GLP-1 overexpression organoids built in this study may provide a novel strategy for the treatment of type 2 diabetes.

Key words： GLP-1; type 2 diabetes; intestinal organoids

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