title: Construction of a Fusion Peptide 5rolGLP-HV and Analysis of its Therapeutic Effect on Type 2 Diabetes Mellitus and Thrombosis in Mice.
abstract: Glucagon-like peptide-1 (GLP-1), is currently used to treat type 2 diabetes mellitus and hirudin (HV), plays an important role in controlling thrombosis and cardiovascular diseases. This investigation aimed to develop a fusion peptide 5rolGLP-HV which combined functions of rolGLP-1 and rHV to treat diabetes and thrombosis. In this study, we constructed a fusion gene including five copies of rolGLP-1 and one copy of rHV (5rolGLP-HV). The optimum expression conditions of 5rolGLP-HV in a soluble form were 0.8 mM IPTG induction when OD600 reached 0.6-0.8 and further growing at 25 °C for 9 h. Isolated rolGLP-1 and rHV were acquired by trypsin digestion in vitro, and the concentration of them was determined by HPLC in vivo. Oral administration of 5rolGLP-HV significantly decreased the levels of blood glucose, GHbA1C, TC, and TG in diabetic mice at the time of 3 weeks compared to the saline-treated group (p < 0.05), while the insulin level was reversed significantly (p < 0.05). 5rolGLP-HV treatment significantly shortened the length of thrombus in thrombosis mice compared to the saline-treated group (p < 0.01). These results indicated that 5rolGLP-HV had dual-function in treating diabetes and preventing thrombosis.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, 300071, Tianjin, China.|Key Laboratory for Bioactive Materials of the Ministry of Education, Institute of Molecular Biology, College of Life Science, Nankai University, 300071, Tianjin, China.
authors.forename: Zaizhong
authors.initials: Z
authors.lastname: Ni
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, 300071, Tianjin, China.|Key Laboratory for Bioactive Materials of the Ministry of Education, Institute of Molecular Biology, College of Life Science, Nankai University, 300071, Tianjin, China.
authors.forename: Yaofang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, 300071, Tianjin, China.|Key Laboratory for Bioactive Materials of the Ministry of Education, Institute of Molecular Biology, College of Life Science, Nankai University, 300071, Tianjin, China.
authors.forename: Haisong
authors.initials: H
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, 300071, Tianjin, China.|Key Laboratory for Bioactive Materials of the Ministry of Education, Institute of Molecular Biology, College of Life Science, Nankai University, 300071, Tianjin, China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, 300071, Tianjin, China.|Key Laboratory for Bioactive Materials of the Ministry of Education, Institute of Molecular Biology, College of Life Science, Nankai University, 300071, Tianjin, China.
authors.forename: Baicheng
authors.initials: B
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, 300071, Tianjin, China.|Key Laboratory for Bioactive Materials of the Ministry of Education, Institute of Molecular Biology, College of Life Science, Nankai University, 300071, Tianjin, China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Hao
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, 300071, Tianjin, China.|Key Laboratory for Bioactive Materials of the Ministry of Education, Institute of Molecular Biology, College of Life Science, Nankai University, 300071, Tianjin, China.
authors.forename: Peipei
authors.initials: P
authors.lastname: Tu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, 300071, Tianjin, China.|Key Laboratory for Bioactive Materials of the Ministry of Education, Institute of Molecular Biology, College of Life Science, Nankai University, 300071, Tianjin, China.
authors.forename: Huikun
authors.initials: H
authors.lastname: Duan
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, 300071, Tianjin, China.|Key Laboratory for Bioactive Materials of the Ministry of Education, Institute of Molecular Biology, College of Life Science, Nankai University, 300071, Tianjin, China.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, 300071, Tianjin, China.|Key Laboratory for Bioactive Materials of the Ministry of Education, Institute of Molecular Biology, College of Life Science, Nankai University, 300071, Tianjin, China.
authors.forename: Pingzhe
authors.initials: P
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, 300071, Tianjin, China.|Key Laboratory for Bioactive Materials of the Ministry of Education, Institute of Molecular Biology, College of Life Science, Nankai University, 300071, Tianjin, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, 300071, Tianjin, China.|Key Laboratory for Bioactive Materials of the Ministry of Education, Institute of Molecular Biology, College of Life Science, Nankai University, 300071, Tianjin, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, 300071, Tianjin, China.|Key Laboratory for Bioactive Materials of the Ministry of Education, Institute of Molecular Biology, College of Life Science, Nankai University, 300071, Tianjin, China.
authors.forename: Ri
authors.initials: R
authors.lastname: Wu
authors.affiliation: Department of Preventive Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, 300071, Tianjin, China. mgl@nankai.edu.cn.|Key Laboratory for Bioactive Materials of the Ministry of Education, Institute of Molecular Biology, College of Life Science, Nankai University, 300071, Tianjin, China. mgl@nankai.edu.cn.|Life Science College, Nankai University, No. 94, Weijin Road, Nankai District, 300071, Tianjin, China. mgl@nankai.edu.cn.
authors.forename: Minggang
authors.initials: M
authors.lastname: Li
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000737:chemistry; D001786:Blood Glucose; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics*; D006629:Hirudins / Q000008:administration & dosage / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000097:blood; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000737:chemistry* / Q000235:genetics; D013927:Thrombosis / Q000188:drug therapy*
chemical_list: C000613574:5rolGLP-HV fusion peptide; D000925:Anticoagulants; D001786:Blood Glucose; D006629:Hirudins; D007328:Insulin; D011993:Recombinant Fusion Proteins; D052216:Glucagon-Like Peptide 1
keywords: 5rolGLP-HV; Diabetes; Dual-function treatment; Expression; Purification; Thrombosis