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

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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Correspondence to Takashi Ikejima.

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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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Keywords

  • Silibinin
  • Palmitic acid
  • Estrogen receptors (ERs)
  • Mitochondria