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Fibroblast growth factor 21: a novel long-acting hypoglycemic drug for canine diabetes

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Abstract

Currently, insulin is commonly used in the clinical management of canine diabetes. However, it must be injected preprandially causing much inconvenience to the owners. Therefore, the development of long-acting hypoglycemic agents has attracted much attention in the scientific community. This study aimed to investigate the long-acting hypoglycemic effect of canine fibroblast growth factor 21 (cFGF-21) in diabetic dogs. Diabetic dogs were administered with cFGF-21, polyethylene glycol-modified cFGF-21 (PEG-cFGF-21), or insulin once a day, once every 2, 3, or 4 days subcutaneously. The results showed that cFGF-21 and PEG-cFGF-21 maintained blood glucose comparable to normal levels for 2 and 3 days respectively while insulin maintained the blood glucose for only 2 h after a single injection. After treatment with cFGF-21, oral glucose tolerance test (OGTT) was significantly improved with glycosylated hemoglobin (HbA1c) close to the normal levels. In addition, cFGF-21 significantly repaired islet β cells, increased insulin content, and protected the pancreas from streptozotocin-induced injury. Furthermore, cFGF-21 exhibited both antioxidant and anti-inflammatory properties in the pancreas. We conclude, therefore, that cFGF-21 and PEG-cFGF-21 can maintain blood glucose comparable to normal levels for 2 and 3 days respectively after a single dose. The long-acting efficacy of cFGF-21 can be attributed to improvement in oxidative stress and the reduction of inflammation in the pancreas.

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Funding

This work was supported by the National Key R&D Program of China [grant numbers 2017YFD0501102, 2017YFD0501004, 2016YFD0501003]; Education Department of Heilongjiang Province [grant number TSTAU-R2018017]; and Science and Technology Department of Heilongjiang Province [grant number GX18B018].

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Authors and Affiliations

  1. Biopharmaceutical Lab., College of Life Science, Northeast Agricultural University, 600 Changjiang Road, Harbin, 150030, China

    Xinghao Jiang, Shijie Liu, Yaoqun Wang, Ruonan Zhang, Yeboah Kwaku Opoku, Yinzhuo Xie, Deshan Li & Guiping Ren

  2. Shanghai Hailu Biological Co., Ltd, Shanghai, 200000, China

    Yaoqun Wang

  3. Department of Biology Education, Faculty of Science Education, University of Education, Winneba, Ghana

    Yeboah Kwaku Opoku

  4. Jiangsu Kanion Pharmaceut CO LTD, State Key Lab New Tech Chinese Med Pharmaceut Pro, Lianyungang, Jiangsu, China

    Deshan Li

  5. Biopharmaceutical Teaching and Research Section, College of Life Science, Northeast Agricultural University, 600 Changjiang Road, Harbin, 150030, China

    Guiping Ren

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  1. Xinghao Jiang
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  2. Shijie Liu
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  3. Yaoqun Wang
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  4. Ruonan Zhang
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  6. Yinzhuo Xie
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  7. Deshan Li
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Contributions

All authors contributed to the study conception, design, and execution. Deshan Li and Guiping Ren designed the study. Xinghao Jiang, Shijie Liu, Yaoqun Wang, and Ruonan Zhang performed the research. Yinzhuo Xie analyzed the data and Yeboah Kwaku Opoku wrote the paper. All authors read and approved the final manuscript. The authors declare that all data were generated in-house and no paper mill was used.

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Correspondence to Guiping Ren.

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The protocols for all the animal experiments were approved by the Animal Care and Use Committee of the Institute of Materia Medica, China.

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Jiang, X., Liu, S., Wang, Y. et al. Fibroblast growth factor 21: a novel long-acting hypoglycemic drug for canine diabetes. Naunyn-Schmiedeberg's Arch Pharmacol 394, 1031–1043 (2021). https://doi.org/10.1007/s00210-020-02023-9

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  • DOI: https://doi.org/10.1007/s00210-020-02023-9

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