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Appl Biochem Biotechnol. 2016 Apr;179(1):59-74. doi: 10.1007/s12010-016-1979-x. Epub 2016 Jan 16.

Construction of a Fusion Peptide 5rolGLP-HV and Analysis of its Therapeutic Effect on Type 2 Diabetes Mellitus and Thrombosis in Mice.

Ni Z1,2, Zhang Y1,2, Wang H1,2, Wei Y1,2, Ma B1,2, Hao J1,2, Tu P1,2, Duan H1,2, Li X1,2, Jiang P1,2, Ma X1,2, Wang B1,2, Wu R1,2, Zhu J3, Li M4,5,6.

Author information

1
State Key Laboratory of Medicinal Chemical Biology, Nankai University, 300071, Tianjin, China.
2
Key Laboratory for Bioactive Materials of the Ministry of Education, Institute of Molecular Biology, College of Life Science, Nankai University, 300071, Tianjin, China.
3
Department of Preventive Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
4
State Key Laboratory of Medicinal Chemical Biology, Nankai University, 300071, Tianjin, China. mgl@nankai.edu.cn.
5
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.
6
Life Science College, Nankai University, No. 94, Weijin Road, Nankai District, 300071, Tianjin, China. mgl@nankai.edu.cn.

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.

KEYWORDS:

5rolGLP-HV; Diabetes; Dual-function treatment; Expression; Purification; Thrombosis

PMID:
26780765
DOI:
10.1007/s12010-016-1979-x
[Indexed for MEDLINE]

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