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转录因子 MEOX 对胰高血糖素样肽 1 分泌细胞中胰岛素基因表达的影响。

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

机构信息

College of Pharmacy and Research Institute of Pharmaceutical Science, Gyeongsang National University, Jinju, 52828, Republic of Korea.

Division of Applied Life Science (BK21 Four), Institute of Agricultural and Life Science, Plant Molecular Biology and Biotechnology Research Center, Plant Biological Rhythm Research Center, Research Institute of Life Science, Gyeongsang National University, Jinju, 52828, Republic of Korea.

出版信息

In Vitro Cell Dev Biol Anim. 2024 Oct;60(9):1099-1108. doi: 10.1007/s11626-024-00964-6. Epub 2024 Aug 13.

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.

摘要

目前,用于治疗 1 型糖尿病的胰岛移植中β细胞的供应受到限制。肠内分泌细胞(EEC)被认为具有很高的干细胞潜力,因为它们与β细胞具有显著的发育相似性。在之前的研究中,我们从 STC-1 细胞中分离出了分泌单个肠道激素的 EEC 细胞。本研究旨在检查肠激素的分泌和表达,研究发育相关转录因子的表达,并分析 MEOX 对分离的 EEC 中胰岛素基因表达的影响。从 STC-1 细胞的 L6 和 K34 细胞中评估肠内分泌激素的表达和分泌。比较 L6 和 K34 细胞与β细胞中β细胞和发育相关基因的表达模式。研究了 MEOX 诱导的β细胞和 GLP-1 分泌细胞中 Ins 表达的比较。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。之前的微阵列分析证实 MEOX 是在β细胞中表达的与发育相关的转录因子。过表达 MEOX 显示出增加 L6 和 GLUTag 细胞中 Ins 表达的趋势,但在 MIN6 细胞中没有。然而,当 PDX1 和 MEOX 在 GLUTag 细胞中共表达时,胰岛素表达被抑制,类似于 MIN6 细胞。这些发现表明 MEOX 在调节β细胞和 GLP-1 分泌细胞中 Ins 基因的表达中具有潜在作用。需要进一步的研究来阐明潜在的机制。

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