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Effects of GW002, a novel recombinant human glucagon-like peptide-1 (GLP-1) analog fusion protein, on CHO recombinant cells and BKS-db mice

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Abstract

Aims

GLP-1-based strategies have many advantages in treatment of type 2 diabetes mellitus (T2DM), but native GLP-1 has a short half-life in the circulation, which limits its clinical application. The purpose of this study was to evaluate the effects of GW002, a novel recombinant GLP-1 analog fusion protein produced by linking the human GLP-1 analog C-terminus to the N-terminus of human serum albumin via a linker, in vitro and in BKS-db mice.

Methods

To determine whether GW002 can activate the GLP-1 receptor in cells, the level of luciferase expression was evaluated in vitro. In vivo, body weight, food intake, non-fasting and fasting blood glucose, oral glucose tolerance test, blood glucose and insulin levels, liver histology, liver function parameters and antibody levels in BKS-db mice were investigated to evaluate the effects of GW002. Albiglutide was chosen as a positive comparator.

Results

Cyclic adenosine monophosphate levels were increased in a dose-dependent manner in cells. In vivo studies demonstrated that GW002 lowers non-fasting and fasting blood glucose levels and improves glucose tolerance and insulin secretion in BKS-db mice. The degree of hepatic steatosis and hepatic biochemical indexes was also decreased. In this study, the mice body weight was not reduced significantly.

Conclusions

The above results showed that the efficacy of GW002 in BKS-db mice displayed a significant hypoglycemic effect, which indicated that GW002 might be a potential candidate for the treatment of T2DM.

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Acknowledgements

The authors would like to thank Peng Fang, Mei-Fang Ma, Qiu-Yun Du and Xiao-Bo Sheng for technical support.

Funding

Funding was provided by Ministry of Science and Technology of P. R. China (No. 2012ZX09401008).

Author information

Author notes

  1. Wan-Wan Ji and Dong-An Yu have contributed equally to this work.

Authors and Affiliations

  1. Jiangsu T-mab BioPharma Co., Ltd, G03, 1# Yao-Cheng Avenue, Taizhou, Jiangsu, People’s Republic of China

    Wan-Wan Ji, Dong-An Yu, Min Fan, Meng You, You Lu, Ning Xie & Shou-Sheng Yan

  2. Nanjing Biomedical Research Institute of Nanjing University, 12#, Xue-Fu Road, Nanjing, Jiangsu, People’s Republic of China

    Er-Bing Li

Authors
  1. Wan-Wan Ji
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  2. Dong-An Yu
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  3. Min Fan
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  4. Meng You
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  5. You Lu
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Correspondence to Shou-Sheng Yan.

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The authors declare that they have no conflict of interest.

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Some datasets generated during and analyzed during the current study are not publicly available due to the commercial secrets but are available from the corresponding author on reasonable request.

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This article does not contain any studies with human subjects performed by the any of the authors.

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Ji, WW., Yu, DA., Fan, M. et al. Effects of GW002, a novel recombinant human glucagon-like peptide-1 (GLP-1) analog fusion protein, on CHO recombinant cells and BKS-db mice. Acta Diabetol 54, 685–693 (2017). https://doi.org/10.1007/s00592-017-0992-z

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