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Silibinin ameliorates amylin-induced pancreatic β-cell apoptosis partly via upregulation of GLP-1R/PKA pathway

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Abstract

The objective was to investigate the mechanism of the protective effect of silibinin on amylin/Aβ1−42-induced INS-1 cell apoptosis, with special reference to the roles of glucagon-like peptide-1 receptor (GLP-1R) and protein kinase A (PKA). The effects of silibinin on apoptosis, insulin secretion, GLP-1R, and PKA expression in the INS-1 cells treated with amylin/Aβ1−42 were examined. INS-1 cells exposed to amylin showed increased TUNEL-positive ratio, reduced expression of GLP-1R and PKA. GLP-1R antagonists or PKA inhibitor enhanced the expression of apoptosis-associated proteins and TUNEL-positive ratio. Silibinin exerted antiapoptotic effect on and upregulation of GLP-1R and PKA. However, Aβ1−42-induced INS-1 cell apoptosis, GLP-1R, and PKA expressions were not changed. Our results indicate that down-regulation of GLP-1R and PKA contributes to INS-1 cell apoptosis induced with amylin. Silibinin protects INS-1 cells from amylin-induced apoptosis through activation of GLP-1R/PKA signaling. Silibinin’s inhibition of the toxic effects of Aβ1−42 is independent of GLP-1R/PKA pathway.

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Acknowledgements

This study was supported by Innovation and Entrepreneurship Training Program of Shenyang Pharmaceutical University (201710163000006), Foundation of Liaoning Education Committee (51120427), and Doctoral Starting up Foundation of Liaoning Science and Technology Department (51120390).

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Authors and Affiliations

  1. Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning, People’s Republic of China

    Jing Yang, Yue Sun, Fanxing Xu, Weiwei Liu, Yingsi Mai, Toshihiko Hayashi & Takashi Ikejima

  2. Department of Chemistry and Life Science, School of Advanced Engineering, Kogakuin University, 2665-1, Nakanomachi, Hachioji, Tokyo, 192-0015, Japan

    Toshihiko Hayashi

  3. Nippi Research Institute of Biomatrix, Toride, Ibaraki, 302-0017, Japan

    Shunji Hattori & Yuko Ushiki-Kaku

  4. Department of Clinical and Biomedical Sciences, Showa Pharmaceutical University, Tokyo, 194-8543, Japan

    Satoshi Onodera

  5. Department of Medical Education and Primary Care, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan

    Shin-ichi Tashiro

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  1. Jing Yang
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Yang, J., Sun, Y., Xu, F. et al. Silibinin ameliorates amylin-induced pancreatic β-cell apoptosis partly via upregulation of GLP-1R/PKA pathway. Mol Cell Biochem 452, 83–94 (2019). https://doi.org/10.1007/s11010-018-3414-9

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