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首页> 外文期刊>BMC Biotechnology >Engineering an L-cell line that expresses insulin under the control of the glucagon-like peptide-1 promoter for diabetes treatment
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Engineering an L-cell line that expresses insulin under the control of the glucagon-like peptide-1 promoter for diabetes treatment

机译：在胰高血糖素样肽-1启动子的控制下工程改造表达胰岛素的L细胞系，以治疗糖尿病

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Background Diabetes mellitus is a complicated disease with a pathophysiology that includes hyperinsulinemia, hyperglycemia and other metabolic impairments leading to many clinical complications. It is necessary to develop appropriate treatments to manage the disease and reduce possible acute and chronic side effects. The advent of gene therapy has generated excitement in the medical world for the possible application of gene therapy in the treatment of diabetes. The glucagon-like peptide-1 ( GLP-1 ) promoter, which is recognised by gut L-cells, is an appealing candidate for gene therapy purposes. The specific properties of L-cells suggest that L-cells and the GLP-1 promoter would be useful for diabetes therapy approaches. Results In this study, L-cells were isolated from a primary intestinal cell line to create suitable target cells for insulin expression studies. The isolated cells displayed L-cell properties and were therefore used as an L-cell surrogate. Next, the isolated L-cells were transfected with the recombinant plasmid consisting of an insulin gene located downstream of the GLP-1 promoter. The secretion tests revealed that an increase in glucose concentration from 5 mM to 25 mM induced insulin gene expression in the L-cells by 2.7-fold. Furthermore, L-cells quickly responded to the glucose stimulation; the amount of insulin protein increased 2-fold in the first 30 minutes and then reached a plateau after 90 minutes. Conclusion Our data showed that L-cells efficiently produced the mature insulin protein. In addition, the insulin protein secretion was positively regulated with glucose induction. In conclusion, GLP-1 promoter and L-cell could be potential candidates for diabetes gene therapy agents.
机译：背景技术糖尿病是一种复杂的疾病，其病理生理学包括高胰岛素血症，高血糖症和其他代谢障碍，导致许多临床并发症。有必要开发适当的治疗方法来控制疾病并减少可能的急性和慢性副作用。基因治疗的出现在医学界引起了人们对于基因治疗在糖尿病治疗中的可能应用的兴奋。肠L细胞识别的胰高血糖素样肽-1（GLP-1）启动子是用于基因治疗的诱人候选物。 L细胞的特殊性质表明，L细胞和GLP-1启动子可用于糖尿病治疗方法。结果在这项研究中，从原肠细胞系中分离出L细胞，以创建适合胰岛素表达研究的靶细胞。分离的细胞表现出L细胞特性，因此被用作L细胞替代物。接下来，将分离的L细胞用由位于GLP-1启动子下游的胰岛素基因组成的重组质粒转染。分泌测试表明，葡萄糖浓度从5 mM增加到25 mM可以诱导L细胞中胰岛素基因表达增加2.7倍。此外，L细胞对葡萄糖刺激迅速作出反应。胰岛素蛋白的量在前30分钟增加了2倍，然后在90分钟后达到稳定水平。结论我们的数据表明L细胞有效地产生了成熟的胰岛素蛋白。此外，葡萄糖诱导正调节胰岛素蛋白的分泌。总之，GLP-1启动子和L细胞可能是糖尿病基因治疗药物的潜在候选者。

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