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，... More
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.
