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Attenuating effect of silibinin on palmitic acid-induced apoptosis and mitochondrial dysfunction in pancreatic β-cells is mediated by estrogen receptor alpha

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Abstract

High levels of circulating free fatty acids often trigger pancreatic β cell dysfunction during the development of type 2 diabetes. Silibinin, the main component of Silybum marianum fruit extract (silymarin), is reported to have anti-diabetic effect. This study is designed to determine the protective effect of silibinin on palmitic acid-induced damage in a rat pancreatic β-cell line, INS-1 cells. Our results demonstrate that silibinin improves cell viability, enhances insulin synthesis and secretion, and resumes normal mitochondrial function in palmitic acid-treated INS-1 cells. An accumulating body of evidence has shown that the estrogen receptors are key molecules involved in glucose and lipid metabolism. Our results suggest that silibinin upregulates ERα signaling pathway from the finding that ERα-specific inhibitors abolish the anti-lipotoxic effect of silibinin. In conclusion, these findings suggest that silibinin protects INS-1 cells against apoptosis and mitochondrial damage through upregulation of ERα pathway.

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Acknowledgements

This research was supported by National Natural Science Foundation of China (No. 81703528).

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Authors and Affiliations

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

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

  2. School of Traditional Chinese Medica, Shenyang Pharmaceutical University, Shenyang, 110016, People’s Republic of China

    Guodong Yao

  3. Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning, People’s Republic of China

    Guodong Yao & Takashi Ikejima

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

    Toshihiko Hayashi

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

    Satoshi Onodera

  6. Department of Pharmacy, The Third People’s Hospital of Chengdu, Chengdu, 610031, Sichuan, People’s Republic of China

    Jing Yang

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  1. Yue Sun
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Sun, Y., Yang, J., Liu, W. et al. Attenuating effect of silibinin on palmitic acid-induced apoptosis and mitochondrial dysfunction in pancreatic β-cells is mediated by estrogen receptor alpha. Mol Cell Biochem 460, 81–92 (2019). https://doi.org/10.1007/s11010-019-03572-1

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