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Artesunate protects pancreatic beta cells against cytokine-induced damage via SIRT1 inhibiting NF-κB activation

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Abstract

Aim

Artesunate (ART) has been known as the most effective and safe reagents to treat malaria for many years. In this study, we explored whether ART could protect pancreatic beta-cell against cytokine-induced damage.

Materials and methods

The production of nitrite (NO) was detected with the Griess Assay Kit. SIRT1 and inducible nitric oxide synthase (iNOS) expression were determined with Western blot. The transcriptional activity of NF-κB was evaluated by luciferase reporter assay. The expression of Sirt1 was silenced by RNA interference. Glucose-stimulated insulin secretion (GSIS) and potassium-stimulated insulin secretion (KSIS) assays were performed to measure the effect of ART on pancreatic beta-cells’ function. The effect of ART on beta-cells apoptosis was evaluated by using Hochest/PI staining and TUNEL assay.

Results

ART enhanced GSIS (KSIS) and reduced apoptosis of pancreatic beta-cells induced by IL-1β. Further study showed that ART inhibited IL-1β-induced increase of NF-κB activity, iNOS expression, and NO production. Moreover, ART up-regulated SIRT1 expression in INS-1 cells and islets exposed to IL-1β. Inhibition of SIRT1 expression could partially abolished the inhibitory effect of ART on NF-κB activity in IL-1β-treated beta-cells. More importantly, the protective effect of ART on cytokine-induced damage was reversed by silencing SIRT1 expression.

Conclusions

ART can elicit a protective effect on beta-cells exposed to IL-1β by stimulating SIRT1 expression, which resulted in the decrease of NF-κB activity, iNOS expression, and NO production. Hence, ART might be an effective drug for diabetes.

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Abbreviations

ART:

Artesunate

GSIS:

Glucose-stimulates insulin secretion

KSIS:

Potassium-stimulated insulin secretion

KRB:

Krebs-Ringer bicarbonate

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

iNOS:

Inducible nitric oxide synthase

NO:

Nitrite

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This study was carried out in accordance with the guidelines of the Institutional Animal Care and Use Committee at Nanjing Medical University and was approved by the Committee on the Ethics of Animal Experiments of Nanjing Medical University.

Informed consent

This study does not involve human subjects.

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Author notes

    Authors and Affiliations

    1. Department of Pathology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, 210029, Jiangsu, China

      L. Yu, X. Shuai, Y. Xu, Y. Ding & D. Su

    2. Department of Endocrinology, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, China

      J. F. Chen

    3. Department of Laboratory Medicine, Jiangsu Province Hospital on Integration of Chinese and Western Medicine, Nanjing, China

      J. Zhang & W. Yang

    4. The Center of Metabolic Disease Research, Nanjing Medical University, 140 Hanzhong Road, Nanjing, 210029, Jiangsu, China

      X. Liang

    5. Department of Endocrinology, Clinical Medical College of Yangzhou University, Yangzhou, 225001, Jiangsu, China

      C. Yan

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    1. L. Yu
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    Correspondence to D. Su or C. Yan.

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    L. Yu and J. Chen contributed equally to this work.

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    Yu, L., Chen, J.F., Shuai, X. et al. Artesunate protects pancreatic beta cells against cytokine-induced damage via SIRT1 inhibiting NF-κB activation. J Endocrinol Invest 39, 83–91 (2016). https://doi.org/10.1007/s40618-015-0328-1

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    • DOI: https://doi.org/10.1007/s40618-015-0328-1

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