Glucagon-like peptide-1 and gastrin synergistically promote the differentiation of insulin-producing cells

Q4 Medicine

中华内分泌代谢杂志 Pub Date : 2020-02-25 DOI:10.3760/CMA.J.ISSN.1000-6699.2020.02.010

Shufang Yan, W. Pang, Huijuan Yuan

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引用次数: 0

Abstract

Objective Glucagon-like peptide-1(GLP-1) and gastrin synergistically promote the differentiation of insulin-producing cells which differentiated from rat bone marrow mesenchymal stem cells (BMSCs). Methods (1)Prepare IPCs model: pancreatic duodenal homeobox 1 (Pdx-1), neurogenin 3 (Ngn3) combined with V-type tendon fibrosarcoma oncogene homolog A (MafA) co-transfected BMSCs differentiation into IPCs; (2)IPCs were divided into 4 groups: Group A(uninduced group), group B(GLP-1 induction group), group C(gastrin induction group), and group D(GLP-1 combined with gastrin induction group). Cultured in high glucose medium for 7 days, the expression levels of insulin2, Pdx-1, GK, nestin, and glucagon mRNA were detected by RT-PCR. The insulin secretion of each group was detected by ELISA. Results After cultured for 7 days under high glucose conditions, the morphology of IPCs in each induction group changed significantly, gradually aggregated and formed scattered cell masses, and the combined induction group formed large cell masses. The staining of disulfide brown was reddish brown; The levels of insulin secretion increased gradually on the 0, 3rd, 5th, 7th, and 9th day after induction, and the increase was the most significant in the combined induction group (P<0.05). Compared with group A, the expression of insulin2 and GK in group B and D was significantly up-regulated, the expression of glucagon was down-regulated in group D, the expression of Pdx-1 was down-regulated in group C, and the expression of glucagon was up-regulated (P<0.05). Compared with group B, The expression of insulin2 was down-regulated in group C, and the expression level of glucagon was up-regulated. The expression levels of Pdx-1 and Insulin2 were significantly up-regulated in group D, and the expression level of glucagon was down-regulated (P<0.05). Compared with group C, the expression level of Pdx-1, insulin2 and GK was significantly up-regulated in group D, and the expression level of glucagon was down-regulated (P<0.05). Conclusion GLP-1 and gastrin synergistically promote the differentiation of IPCs into islet β cells by up-regulating GK and insulin2 and down-regulating glucagon. Key words: Glucagon-like peptide 1; Gastrin; Pancreatic duodenal homeobox 1; Neurogenin 3; V-type tendon fibrosarcoma oncogene homologous gene A; Insulin-producing cells

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胰高血糖素样肽-1和胃泌素协同促进胰岛素生成细胞的分化

目的胰高血糖素样肽-1（GLP-1）和胃泌素协同促进大鼠骨髓间充质干细胞分化为胰岛素产生细胞。方法（1）制备IPCs模型：胰十二指肠同源盒1（Pdx-1）、神经蛋白3（Ngn3）联合V型肌腱纤维肉瘤癌基因同源物A（MafA）共转染BMSCs分化为IPCs；（2） IPCs分为4组：A组（未诱导组）、B组（GLP-1诱导组），C组（胃泌素诱导组）和D组（GLP-1+胃泌素诱导组。在高糖培养基中培养7天，通过RT-PCR检测胰岛素2、Pdx-1、GK、巢蛋白和胰高血糖素mRNA的表达水平。ELISA法检测各组胰岛素分泌情况。结果在高糖条件下培养7天后，各诱导组IPCs的形态发生显著变化，逐渐聚集形成分散的细胞团，联合诱导组形成较大的细胞团。二硫化物褐色染色为红褐色；胰岛素分泌水平在诱导后0、3、5、7和9天逐渐增加，其中联合诱导组的增加最为显著（P<0.05）。与A组相比，B和D组胰岛素2和GK的表达显著上调，D组胰高血糖素的表达下调，C组Pdx-1表达下调，胰高血糖素表达上调（P<0.05）。与B组相比，C组胰岛素2表达下调，血糖素表达水平上调。D组Pdx-1和Insulin2的表达水平显著上调，胰高血糖素的表达水平下调（P<0.05）。与C组相比，D组Pdx-1、Insulin2和GK的表达水平明显上调，结论GLP-1和胃泌素通过上调GK和胰岛素2，下调胰高血糖素，协同促进IPC向胰岛β细胞分化。关键词：胰高血糖素样肽1；胃泌素；胰十二指肠同源盒1；神经生成素3；V型肌腱纤维肉瘤癌基因同源基因A；胰岛素产生细胞

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来源期刊

中华内分泌代谢杂志 Medicine-Endocrinology, Diabetes and Metabolism

CiteScore

0.60

自引率

0.00%

发文量

7243

期刊介绍： The Chinese Journal of Endocrinology and Metabolism was founded in July 1985. It is a senior academic journal in the field of endocrinology and metabolism sponsored by the Chinese Medical Association. The journal aims to be the "Chinese broadcaster of new knowledge on endocrinology and metabolism worldwide". It reports leading scientific research results and clinical diagnosis and treatment experience in endocrinology and metabolism and related fields, as well as basic theoretical research that has a guiding role in endocrinology and metabolism clinics and is closely integrated with clinics. The journal is a core journal of Chinese science and technology (a statistical source journal of Chinese science and technology papers), and is included in Chinese and foreign statistical source journal databases such as the Chinese Science and Technology Papers and Citation Database, Chemical Abstracts, and Scopus.