Glucagon-like peptide-1 plasmid construction and delivery for the treatment of type 2 diabetes
Glucagon-like peptide-1 plasmid construction and delivery for the treatment of type 2 diabetes
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DOI：
10.1016/j.ymthe.2005.03.039
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发表时间：
2005-11-01
影响因子：
12.4
通讯作者：
Kim, SW
中科院分区：
文献类型：
--
作者：
Choi, S;Oh, S;Kim, SW
胰升糖素样肽-1(GLP-1)是由肠道L细胞产生的一种由30个氨基酸组成的激素。GLP-1被认为是一种新的治疗2型糖尿病的药物，因为它具有促进胰岛素分泌的作用，并且在2型糖尿病患者中保持有效。尽管GLP-1作为糖尿病的治疗药物具有许多显著的优点，但由于其极短的半衰期，并不能立即应用于临床。克服这一缺陷的一种方法是GLP1基因传递，它使GLP-1能够在体内产生。本研究利用GLP1(7-37)基因构建的新载体，在体内外对GLP1基因的导入效果进行了评价。GLP1基因的表达由SV40启动子/增强子驱动。为了提高GLP-1的表达水平，引入了核因子-kappaB结合位点。体外实验结果表明，GLP-1的表达和GLP-1的体外活性是一种葡萄糖依赖的胰岛素样作用。单次全身注射聚乙烯亚胺/pSIGLP1NF-kappa B复合体后，DIO小鼠胰岛素分泌增加，血糖水平下降，持续时间超过2周。
Glucagon-like peptide-1 (GLP-1) is a 30-amino-acid hormone produced by intestinal L cells. It has been proposed that GLP-1 can be used as a new treatment for type 2 diabetes mellitus because it acts to augment insulin secretion and its effectiveness is maintained in type 2 diabetic patients. Despite its many remarkable advantages as a therapeutic agent for diabetes, GLP-1 is not immediately clinically applicable because of its extremely short half-life. One way to overcome this drawback is GLP1 gene delivery, which enables GLP-1 production in the body. In this study, the effect of GLP1 gene delivery was evaluated both in vitro and in vivo using a new plasmid constructed with a GLP1 (7-37) cDNA. The expression of the GLP1 gene was driven by a SV40 promoter/enhancer. To increase the expression level of GLP-1, nuclear factor kappa B binding sites were introduced. The in vitro results showed expression of GLP-1 and in vitro activity of GLP-1, which is a glucose-dependent insulinotropic action. A single systemic administration of polyethyleneimine/pSIGLP1NF kappa B complex into DIO mice resulted in increasing insulin secretion and decreasing blood glucose levels for a duration longer than 2 weeks.