Effect of transcription factor MEOX on insulin gene expression in glucagon-like peptide 1-secreting cells.

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Accounts of Chemical Research Pub Date : 2024-10-01 Epub Date: 2024-08-13 DOI:10.1007/s11626-024-00964-6
Gyeong Ryul Ryu, Dongryeoul Bae, Shahab Uddin, Mohammed Sohel Meah, Waqas Ahmad, Kris John Silvano, Gyeongik Ahn, Joon-Yung Cha, Esder Lee, Ki-Ho Song, Woe-Yeon Kim, Min Gab Kim
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Abstract

Currently, the supply of beta cells for islet transplantation in the treatment of type 1 diabetes is limited. Enteroendocrine cells (EECs) are believed to have high potential as stem cells because they share significant developmental similarities with beta cells. In a previous study, we derived EEC cells that secrete individual gut hormones from STC-1 cells. This study aimed to examine intestinal hormone secretion and expression, investigate the expression of developmental-related transcription factors, and analyze the effect of MEOX on insulin gene expression in isolated EECs. The expression and secretion of enteroendocrine hormones were evaluated in L6 and K34 cells from STC-1 cells. Expression patterns of beta cell- and development-related genes in L6 and K34 cells were compared with beta cells. Comparisons of the MEOX-induced expression of Ins in beta cells and GLP-1-secreting cells were investigated. Both L6 and K34 cells predominantly expressed Glp1 and Gip, respectively. The secretion pattern of GLP-1 in L6 cells was similar to that of GLUTag cells. Previous microarray analysis confirmed MEOX as developmentally relevant transcription factors expressed in beta cells. Overexpression of MEOX showed a tendency to increase Ins expression in L6 and GLUTag cells, but not in MIN6 cells. However, when PDX1 and MEOX were co-expressed in GLUTag cells, insulin expression was suppressed, similar to that observed in MIN6 cells. These findings suggest a potential role for MEOX in regulating the expression of the Ins gene in both beta cells and GLP-1-secreting cells. Further studies are warranted to elucidate the underlying mechanism.

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转录因子 MEOX 对分泌胰高血糖素样肽 1 的细胞中胰岛素基因表达的影响
目前,用于胰岛移植治疗1型糖尿病的β细胞供应有限。肠内分泌细胞(EECs)与β细胞在发育上有很大的相似性,因此被认为具有很大的干细胞潜力。在之前的一项研究中,我们从STC-1细胞中提取了能分泌单个肠道激素的EEC细胞。本研究旨在检测肠道激素的分泌和表达,研究与发育相关的转录因子的表达,并分析MEOX对离体EECs中胰岛素基因表达的影响。研究评估了来自 STC-1 细胞的 L6 和 K34 细胞中肠内分泌激素的表达和分泌情况。将 L6 和 K34 细胞中的β细胞和发育相关基因的表达模式与β细胞进行了比较。研究了MEOX诱导的Ins在β细胞和分泌GLP-1细胞中的表达比较。L6 和 K34 细胞分别主要表达 Glp1 和 Gip。L6 细胞中 GLP-1 的分泌模式与 GLUTag 细胞相似。之前的芯片分析证实,MEOX是β细胞中表达的与发育相关的转录因子。过表达 MEOX 会增加 L6 和 GLUTag 细胞中 Ins 的表达,但不会增加 MIN6 细胞中 Ins 的表达。然而,当 PDX1 和 MEOX 在 GLUTag 细胞中共同表达时,胰岛素的表达受到抑制,这与在 MIN6 细胞中观察到的情况相似。这些发现表明,MEOX 在调节β细胞和 GLP-1 分泌细胞中 Ins 基因的表达方面具有潜在作用。还需要进一步研究以阐明其潜在机制。
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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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