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

• DOI: 10.1007/s12010-016-1979-x
• Publication Date: 2016-01-16T17:34:41Z
• Authors: Zaizhong Ni; Yaofang Zhang; Haisong Wang; Yiming Wei; Baicheng Ma; Junfeng Hao; Peipei Tu; Huikun Duan; Xiaodan Li; Pingzhe Jiang; Xiaofeng Ma; Bin Wang; Ri Wu; Jianhong Zhu; Minggang Li
• Keywords: Blood Glucose; 0303 health sciences; Recombinant Fusion Proteins; Anticoagulants; Thrombosis; Hirudins; 3. Good health; Mice; 03 medical and health sciences; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Animals; Humans; Insulin

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.