Pharmacological Effects and Pharmacokinetic Properties of a Dual-Function Peptide 5rolGLP-HV.
In order to better understand the therapeutic mechanism of dual-function peptide 5rolGLP-HV in treatment of treat diabetes and its complication of thrombosis, the pharmacological effects and pharmacokinetic properties of 5rolGLP-HV were conducted in this study. 5rolGLP-HV was orally administered to diabetic mice, and the hypoglycemic mechanism was investigated. Thrombotic mice were applied to study the thrombus dissolving ability of 5rolGLP-HV. The concentration of rolGLP and rHV in rat plasma following single oral dose or intravenous injection of 5rolGLP-HV was measured. Treatment with 5rolGLP-HV decreased insulin resistance (2.96 ± 1.43 vs. 9.35 ± 1.51, p < 0.05) of diabetic mice. 5rolGLP-HV shortened the length of thrombus in thrombosis mice (2.92 ± 0.74 vs. 5.92 ± 1.16 cm, p < 0.01) and extended the thrombin time (15.35 ± 1.22 vs. 8.67 ± 0.89 s, p < 0.01) of normal mice. Meanwhile, 5rolGLP-HV restored the damage of pancreatic, liver, kidney, and adipose tissues induced in the diabetic mice. 5rolGLP-HV exhibited a fast absorption and slow elimination phase after digested into rolGLP-1 and rHV in vivo. These results suggested that 5rolGLP-HV had an ideal therapeutic potential in the prevention of β cell dysfunction in type 2 diabetes and delay of the thrombus.
State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China.|Key Laboratory for Bioactive Materials of the Ministry of Education, Institute of Molecular Biology, College of Life Science, Nankai University, Tianjin, 300071, China.
Zaizhong
Z
Ni
State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China.|Key Laboratory for Bioactive Materials of the Ministry of Education, Institute of Molecular Biology, College of Life Science, Nankai University, Tianjin, 300071, China.
Xiaofeng
X
Ma
State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China.|Key Laboratory for Bioactive Materials of the Ministry of Education, Institute of Molecular Biology, College of Life Science, Nankai University, Tianjin, 300071, China.
Bin
B
Wang
State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China.|Key Laboratory for Bioactive Materials of the Ministry of Education, Institute of Molecular Biology, College of Life Science, Nankai University, Tianjin, 300071, China.
Haisong
H
Wang
State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China.|Key Laboratory for Bioactive Materials of the Ministry of Education, Institute of Molecular Biology, College of Life Science, Nankai University, Tianjin, 300071, China.
Huikun
H
Duan
State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China.|Key Laboratory for Bioactive Materials of the Ministry of Education, Institute of Molecular Biology, College of Life Science, Nankai University, Tianjin, 300071, China.
Xiaodan
X
Li
State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China.|Key Laboratory for Bioactive Materials of the Ministry of Education, Institute of Molecular Biology, College of Life Science, Nankai University, Tianjin, 300071, China.
Pingzhe
P
Jiang
State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China.|Key Laboratory for Bioactive Materials of the Ministry of Education, Institute of Molecular Biology, College of Life Science, Nankai University, Tianjin, 300071, China.
Peipei
P
Tu
Department of Zoology and Developmental Biology, College of Life Sciences, Nankai University, Tianjin, 300071, China.
Qiang
Q
Zhao
Department of Preventive Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Jianhong
J
Zhu
State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, 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, Tianjin, 300071, China. mgl@nankai.edu.cn.|Life Science College, Nankai University, No. 94, Weijin Road, Nankai District, Tianjin, 300071, China. mgl@nankai.edu.cn.
Minggang
M
Li
D000284:Administration, Oral; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D004338:Drug Combinations; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006629:Hirudins / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D013927:Thrombosis / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D016896:Treatment Outcome
C000613574:5rolGLP-HV fusion peptide; D004338:Drug Combinations; D005343:Fibrinolytic Agents; D006629:Hirudins; D007004:Hypoglycemic Agents; D011993:Recombinant Fusion Proteins; D052216:Glucagon-Like Peptide 1
5rolGLP-HV; Pharmacokinetic; Pharmacological; Thrombosis; Type 2 diabetes mellitus