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

Modified human glucagon-like peptide-1 (GLP-1) produced in E. coli has a long-acting therapeutic effect in type 2 diabetic mice.
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Xu F, Wang KY, Wang N, Li G, Liu D,


Xu F, Wang KY, Wang N, Li G, Liu D, (click to view)

Xu F, Wang KY, Wang N, Li G, Liu D,

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PloS one 2017 07 2712(7) e0181939 doi 10.1371/journal.pone.0181939
Abstract

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, 6×mGLP-1. The purified recombinant 6×mGLP-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 β 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 6×mGLP-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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