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Artemisinin and dihydroartemisinin promote β-cell apoptosis induced by palmitate via enhancing ER stress

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Abstract

Artemisinin (ART) and dihydroartemisinin (DHA) are first-line antimalarial drugs and have been reported to have anti-obesity effects. Hyperlipidemia is associated with β-cell damage in obese subjects, which could contribute to the pathogenesis of type 2 diabetes. In addition to their anti-obesity effects, ART and DHA also have protective roles in some diseases. Thus, we investigated the effects of ART and DHA in palmitate-induced β-cell apoptosis and the underlying mechanism. In this study, the rat pancreatic β-cell line INS-1 and mouse pancreatic β-cell line MIN6 were cultured with palmitate (PA) (0.1 mM) to induce cell apoptosis in the presence or absence of ART or DHA. Cell apoptosis was investigated by using flow cytometry, and the expression of ER stress markers, including CHOP, GRP78 and PDI, was detected by Western blotting and/or qRT-PCR. The results showed that ART and DHA significantly increased the apoptosis of β-cells induced by PA and exacerbated the ER stress caused by PA. An inhibitor of ER stress, 4-phenylbutyric acid (4-PBA), significantly ameliorated cell apoptosis caused by ART and DHA in PA-treated β-cells, consistent with the inhibition of ER stress. Together, the findings from the current study suggested that ART and DHA may promote lipid disorder-associated β-cell injury via enhancing ER stress when they were used to treat obesity.

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Funding

This work was supported by Grants from the Nanjing Science and Technology Commission (ZKX15041) and Nanjing National Commission on Health and Family Planning (ZKX16057).

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  1. Ke Chen, Hu Hua and Ziyang Zhu have contributed equally to this work.

Authors and Affiliations

  1. Department of Endocrinology, Children’s Hospital of Nanjing Medical University, Guangzhou Road #72, Nanjing, 210008, China

    Ke Chen, Ziyang Zhu, Tong Wu & Qianqi Liu

  2. Department of Child Health Care, Children’s Hospital of Nanjing Medical University, Guangzhou Road #72, Nanjing, 210008, China

    Ke Chen, Ziyang Zhu, Tong Wu & Qianqi Liu

  3. Nanjing Key Laboratory of Pediatrics, Children’s Hospital of Nanjing Medical University, Nanjing, 210008, China

    Hu Hua & Zhanjun Jia

  4. Department of Nephrology, Children’s Hospital of Nanjing Medical University, Guangzhou Road #72, Nanjing, 210008, China

    Zhanjun Jia

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  1. Ke Chen
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Chen, K., Hua, H., Zhu, Z. et al. Artemisinin and dihydroartemisinin promote β-cell apoptosis induced by palmitate via enhancing ER stress. Apoptosis 25, 192–204 (2020). https://doi.org/10.1007/s10495-019-01587-z

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