High-Level Expression of Fusion Protein Containing 10 Tandem Repeated GLP-1 Analogs in Yeast Pichia pastoris and Its Biological Activity in a Diabetic Rat Model

HOU, Jianhua; YAN, Ruixiang; Yang, Liquan; Wu, Zhiqiang; Wang, Cuiyan; DING, Dongfeng; Li, Na; MA, Chunxiao; Li, Minggang

High-Level Expression of Fusion Protein Containing 10 Tandem Repeated GLP-1 Analogs in Yeast Pichia pastoris and Its Biological Activity in a Diabetic Rat Model

2007

Glucagon-like peptide-1 (GLP-1), an incretin secreted by intestinal L-cells, can effectively lower blood glucose levels in patients with diabetes. A fusion gene, consisting of 10 tandem repeated GLP-1 analog genes, was expressed at a high level in the yeast Pichia pastoris. SDS polyacrylamide gel electrophoresis (SDS–PAGE), and Western Blotting results showed that fusion protein migrated as a single protein band with a molecular weight of 36 kDa. A biological activity test showed that the GLP-1 analog could significantly lower the level of serum glucose when GLP-1 purified analog was injected into diabetic rats. A potential strategy for large-scale production of fusion protein containing the 10 GLP-1 analogs as discovered, and a single GLP-1 analog was obtained from fusion protein digested with trypsin. This should be inspired foreign expression of medicinal short peptides and be valuable in further research on GLP-1 analog drugs in the treatment of diabetes mellitus.

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