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Pharmacological Effects and Pharmacokinetic Properties of a Dual-Function Peptide 5rolGLP-HV

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Abstract

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.

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Abbreviations

T2DM:

Type 2 diabetes mellitus

DPP-IV:

Dipeptidyl peptidase IV

rolGLP-1:

Recombinant oral long-acting GLP-1

HV:

Hirudin

rHV:

Recombinant hirudin

STZ:

Streptozotocin

FBG:

Fasting blood-glucose

FINS:

Fasting insulin

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Acknowledgments

This study is supported by the Key Technologies R&D Program of Tianjin (14ZCZDSY00013).

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Author notes

  1. Minggang Li

    Present address: Life Science College, Nankai University, No. 94, Weijin Road, Nankai District, Tianjin, 300071, China

Authors and Affiliations

  1. State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China

    Zaizhong Ni, Xiaofeng Ma, Bin Wang, Haisong Wang, Huikun Duan, Xiaodan Li, Pingzhe Jiang, Peipei Tu & Minggang Li

  2. Key Laboratory for Bioactive Materials of the Ministry of Education, Institute of Molecular Biology, College of Life Science, Nankai University, Tianjin, 300071, China

    Zaizhong Ni, Xiaofeng Ma, Bin Wang, Haisong Wang, Huikun Duan, Xiaodan Li, Pingzhe Jiang, Peipei Tu & Minggang Li

  3. Department of Zoology and Developmental Biology, College of Life Sciences, Nankai University, Tianjin, 300071, China

    Qiang Zhao

  4. Department of Preventive Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China

    Jianhong Zhu

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  1. Zaizhong Ni
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Correspondence to Minggang Li.

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Ni, Z., Ma, X., Wang, B. et al. Pharmacological Effects and Pharmacokinetic Properties of a Dual-Function Peptide 5rolGLP-HV. Appl Biochem Biotechnol 181, 483–494 (2017). https://doi.org/10.1007/s12010-016-2225-2

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  • DOI: https://doi.org/10.1007/s12010-016-2225-2

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