Self-inducible secretion of glucagon-like peptide-1 (GLP-1) that allows MIN6 cells to maintain insulin secretion and insure cell survival
Self-inducible secretion of glucagon-like peptide-1 (GLP-1) that allows MIN6 cells to maintain insulin secretion and insure cell survival
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DOI：
10.1016/j.mce.2011.11.008
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发表时间：
2012-02
影响因子：
4.1
通讯作者：
Koji Nakashima;M. Shimoda;Sumiko Hamamoto;F. Tatsumi;H. Hirukawa;K. Tawaramoto;Y. Kanda;K. Kaku
中科院分区：
文献类型：
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作者：
Koji Nakashima;M. Shimoda;Sumiko Hamamoto;F. Tatsumi;H. Hirukawa;K. Tawaramoto;Y. Kanda;K. Kaku
基于MIN6细胞能够产生胰高血糖素样肽-1(GLP-1)维持细胞存活的假设，我们分析了GLP-1受体激动剂Exendin-4(Ex4)和拮抗剂Exendin-(9-39)(Ex9)对细胞功能和细胞分化的影响。MIN6细胞表达胰高血糖素原mRNAs，产生GLP-1，而GLP-1被Ex4促进，Ex9抑制。此外，EX4进一步增强了葡萄糖刺激的GLP-1的分泌，提示自分泌环促进了GLP-1信号的放大。EX4上调与细胞分化和细胞功能相关的CREBBP、PDX-1、Pax6、胰高血糖素原和PC1/3基因的表达。激光共聚焦扫描图像显示，GLP-1阳性细胞在细胞早期占优势，而胰岛素阳性细胞在细胞成熟期更为明显。Ex4促进细胞存活，Ex9和抗GLP-1受体抗体促进细胞凋亡。MIN6细胞具有自分泌的GLP-1信号放大机制，通过这种机制维持胰岛素的产生和细胞的存活。
Based on the hypothesis that MIN6 cells could produce glucagon-like peptide-1 (GLP-1) to maintain cell survival, we analyzed the effects of GLP-1 receptor agonist, exendin-4 (Ex4), and antagonist, exendin-(9–39) (Ex9) on cell function and cell differentiation. MIN6 cells expressed proglucagon mRNAs and produced GLP-1, which was accelerated by Ex4 and suppressed by Ex9. Moreover, Ex4 further enhanced glucose-stimulated GLP-1 secretion, suggesting autocrine loop-contributed amplification of the GLP-1 signal. Ex4 up-regulated cell differentiation- and cell function-related CREBBP, Pdx-1, Pax6, proglucagon, and PC1/3 gene expressions. The confocal laser scanning images revealed that GLP-1 positive cells were dominant in the early stage of cells, but positive for insulin were more prominent in the mature stage of cells. Ex4 accelerated cell viability, while Ex9 and anti-GLP-1 receptor antibody enhanced cell apoptosis. MIN6 cells possess a mechanism of GLP-1 signal amplification in an autocrine fashion, by which the cells maintained insulin production and cell survival.