长效促胰岛素降糖酵母的构建及其对糖尿病模型小鼠的治疗效果

doi:10.16288/j.yczz.14-206

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HEREDITAS(Beijing) ›› 2015, Vol. 37 ›› Issue (2): 183-191.doi: 10.16288/j.yczz.14-206

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Construction of yeast strains expressing long-acting glucagon-like peptide-1 (GLP-1) and their therapeutic effects on type 2 diabetes mellitus mouse model

Ri Wu¹,Chao Ma¹,Xiaodan Li¹,Huikun Duan¹,Yanli Ji¹,Yu Wang¹,Pingzhe Jiang¹,Haisong Wang¹,Peipei Tu¹,Miao Li¹,Ganggang Ni¹,Baicheng Ma²,Minggang Li¹

1. Key Laboratory for Bioactive Materials of the Ministry of Education, Institute of Molecular Biology, College of Life Science, Nankai University, Tianjin 300071, China;
2. Tianjin Children’s Hospital, Tianjin 300074, China

Received:2014-06-25 Online:2015-02-20 Published:2015-01-19

Abstract

Abstract: Probiotics, i.e., bacteria expressing therapeutic peptides (protein), are used as a new type of orally administrated biologic drugs to treat diseases. To develop yeast strains which could effectively prevent and treat type 2 diabetes mellitus, we firstly constructed the yeast integrating plasmid pNK1-PGK which could successfully express green fluorescent protein (GFP) in Saccharomyces cerevisiae. The gene encoding ten tandem repeats of glucagon-like peptide-1(10×GLP-1) was cloned into the vector pNK1-PGK and the resulting plasmids were then transformed into the S. cerevisiae INVSc1. The long-acting GLP-1 hypoglycemic yeast (LHY) which grows rapidly and expresses 10×GLP-1 stably was selected by nutrition screening and Western blotting. The amount of 10×GLP-1 produced by LHY reached 1.56 mg per gram of wet cells. Moreover, the oral administration of LHY significantly reduced blood glucose level in type 2 diabetic mice induced by streptozotocin plus high fat and high sugar diet.

Key words: type 2 diabetes mellitus, glucagon-like peptide-1(GLP-1), long-acting GLP-1 hypoglycemic yeast (LHY), recombinant yeast, mouse model of type 2 diabetes mellitus

Ri Wu,Chao Ma,Xiaodan Li,Huikun Duan,Yanli Ji,Yu Wang,Pingzhe Jiang,Haisong Wang,Peipei Tu,Miao Li,Ganggang Ni,Baicheng Ma,Minggang Li. Construction of yeast strains expressing long-acting glucagon-like peptide-1 (GLP-1) and their therapeutic effects on type 2 diabetes mellitus mouse model[J]. HEREDITAS(Beijing), 2015, 37(2): 183-191.

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Construction of yeast strains expressing long-acting glucagon-like peptide-1 (GLP-1) and their therapeutic effects on type 2 diabetes mellitus mouse model

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