Modified human glucagon-like peptide-1 (GLP-1) produced in E-coli has a long-acting therapeutic effect in type 2 diabetic mice

文献类型： 外文期刊

第一作者： Xu, Fangfang

作者： Xu, Fangfang;Wang, Nan;Li, Gangqiang;Liu, Dehu;Wang, Kevin Yueju

作者机构：

期刊名称：PLOS ONE （ 影响因子：3.24； 五年影响因子：3.788 ）

ISSN： 1932-6203

年卷期： 2017 年 12 卷 7 期

页码：

收录情况： SCI

摘要： Glucagon-like peptide 1 (GLP-1) is a very potent insulinotropic hormone secreted into the blood stream after eating. Thus, it has potential to be used in therapeutic treatment of diabetes. The half-life of GLP-1, however, is very short due to its rapid cleavage by dipeptidyl peptidase IV (DPP-IV). This presents a great challenge if it is to be used as a therapeutic drug. GLP-1, like many other small peptides, is commonly produced through chemical synthesis, but is limited by cost and product quantity. In order to overcome these problems, a sequence encoding a six codon-optimized tandem repeats of modified GLP-1 was constructed and expressed in the E. coli to produce a protease-resistant protein, 6xmGLP-1. The purified recombinant 6xmGLP-1, with a yield of approximately 20 mg/L, could be digested with trypsin to obtain single peptides. The single mGLP-1 peptides significantly stimulated the proliferation of a mouse pancreatic beta cell line, MIN6. The recombinant peptide also greatly improved the oral glucose tolerance test of mice, exerted a positive glucoregulatory effect, and most notably had a glucose lowering effect for as long as 16.7 hours in mice altered to create a type 2 diabetic condition and exerted a positive glucoregulatory effect in db/db mice. These results indicate that recombinant 6xmGLP-1 has great potential to be used as an effective and cost-efficient drug for the treatment of type 2 diabetes.

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