硫氧还蛋白相互作用蛋白降低GLP-1促小鼠胰岛β细胞的增殖效应

基础医学与临床 ›› 2020, Vol. 40 ›› Issue (8): 1076-1082.

硫氧还蛋白相互作用蛋白降低GLP-1促小鼠胰岛β细胞的增殖效应

张文婷, 王瑾, 岳继萍, 靳文文, 张志楠, 焦向英^*

山西医科大学生理学系,山西太原 030001

收稿日期:2019-08-26 修回日期:2019-12-03 出版日期:2020-08-05 发布日期:2020-07-29
通讯作者: ^*jiaoxyty@163.com
基金资助:
山西省面上青年基金 (201801D221401)

TXNIP reduces pro-proliferation effect of GLP-1 on mouse islet β cells

ZHANG Wen-ting, WANG Jin, YUE Ji-ping, JIN Wen-wen, ZHANG Zhi-nan, JIAO Xiang-ying^*

Department of Physiology, Shanxi Medical University, Taiyuan 030001, China

Received:2019-08-26 Revised:2019-12-03 Online:2020-08-05 Published:2020-07-29
Contact: ^*jiaoxyty@163.com

摘要/Abstract

摘要： 目的观察硫氧还蛋白相互作用蛋白(TXNIP)在胰高血糖素样肽-1(GLP-1)促小鼠胰岛β细胞的增殖效应中的作用。方法小鼠分为db/m组和db/db组,每组10只;慢病毒构建TXNIP过表达(Ad-TXNIP-GFP)稳转小鼠胰岛β细胞株MIN6细胞,分为对照组、Ad-GFP组和Ad-TXNIP-GFP组。Western blot检测TXNIP、增殖细胞核抗原(PCNA)和GLP-1受体(GLP-1R)的表达,HE和免疫荧光观察胰岛形态和β细胞数量,GLP-1R、Ki67,ELISA检测小鼠血清中GLP-1的表达,免疫组化检测GLP-1R水平。结果 db/db鼠胰岛形态破坏且β细胞数量减少;胰腺组织PCNA表达降低(P＜0.05);血清GLP-1水平降低(P＜0.05);胰腺组织和胰岛GLP-1R水平降低(P＜0.05);胰腺组织TXNIP表达升高(P＜0.05);TXNIP过表达细胞模型构建成功(P＜0.05);TXNIP过表达时GLP-1R水平降低(P＜0.05);TXNIP过表达使GLP-1对胰岛β细胞的增殖效应降低(P＜0.05)。结论 TXNIP作用于GLP-1R从而降低GLP-1对小鼠胰岛β细胞的增殖效应。

关键词: 硫氧还蛋白相互作用蛋白, GLP-1, GLP-1受体, 细胞增殖

Abstract: Objective To observe the role of thioredoxin interacting protein (TXNIP) in the proliferation of islet β cells promoted by Glucagon-like peptide 1 (GLP-1). Methods The mice were divided into db/m group and db/db group; TXNIP over-expression (Ad-TXNIP-GFP) MIN6 cells were constructed by stably transfected with lentivirus, which were divided into control group, Ad-GFP group and Ad-TXNIP-GFP group. Western blot was used to detect the expression of TXNIP and proliferating cell nuclear antigen (PCNA) in pancreatic tissues of db/m and db/db mice. The morphology of the islets, the number of β cells, GLP-1R and Ki67 were observed by HE and immunohistochemistry method. The expression of GLP-1 in serum was detected by ELISA. The level of GLP-1R protein in pancreatic tissue was detected by immunohistochemistry. Results Islet structure was destructed, the number of β cells and PCNA expression decreased in pancreatic tissue of db/db mice (P＜0.05). The level of GLP-1 in serum reduced (P＜0.05), and the level of GLP-1 receptor in pancreatic tissue and islet was reduced (P＜0.05). The expression of TXNIP in pancreatic tissues of db/db mice increased (P＜0.05). The TXNIP overexpression cell model was successfully constructed (P＜0.05), and the level of GLP-1 receptor decreased in islet β cells (P＜0.05). The overexpression of TXNIP reduced the proliferative effect of islet β cells to GLP-1 (P＜0.05). Conclusions TXNIP acts on the GLP-1 receptor to reduce the proliferation of islet β cells promoted by GLP-1.

Key words: thioredoxin interacting protein, GLP-1, GLP-1 receptor, cell proliferation

中图分类号:

张文婷, 王瑾, 岳继萍, 靳文文, 张志楠, 焦向英. 硫氧还蛋白相互作用蛋白降低GLP-1促小鼠胰岛β细胞的增殖效应[J]. 基础医学与临床, 2020, 40(8): 1076-1082.

ZHANG Wen-ting, WANG Jin, YUE Ji-ping, JIN Wen-wen, ZHANG Zhi-nan, JIAO Xiang-ying. TXNIP reduces pro-proliferation effect of GLP-1 on mouse islet β cells[J]. Basic & Clinical Medicine, 2020, 40(8): 1076-1082.

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