Expression of rolGLP-HV in E. coli and its Dual-Function for the Treatment of Diabetes and Thrombosis

Glucagon-like peptide-1 (GLP-1) reduces blood glucose and improves abnormal metabolism caused by hyperglycemia. The formation of thrombus, one of major consequences suffered from diabetes, can be inhibited by the treatment of Hirudin (HV). This study was aimed to develop a fusion peptide which combines functions of GLP-1 and HV to treat diabetes and its complication thrombosis. A rolGLP-HV expression plasmid was constructed and expressed in BL21 (DE3) line of E. coli. The peptide was then purified and analyzed in vitro and in vivo for its anti-thrombosis ability. The results showed that the anti-coagulant activity of rolGLP-HV was about 109 ± 1.7 ATU/mL, and the peptide displayed a great ability in reducing thrombosis in a mouse model. The effect of rolGLP-HV on plasma glucose was assessed by daily oral-gavage administration up to 10 days in streptozotocin-induced type 2 diabetic mice. Our results showed that rolGLP-HV treatment decreased (p < 0.01) plasma glucose level by 41.6 and 55.7 %, respectively, on the 5th and 10th day post the initial oral gavage. Also, rolGLP-HV treatment led to an increase in body weight and decreases in drink level and food intake (p < 0.05) compared with the control. In conclusion, our data suggest that rolGLP-HV peptide has dual-function in preventing thrombosis and reducing plasma glucose.