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Int J Biol Sci 2019; 15(7):1472-1487. doi:10.7150/ijbs.33817 This issue Cite

Research Paper

Hypericin maintians PDX1 expression via the Erk pathway and protects islet β-cells against glucotoxicity and lipotoxicity

Chen Liang1,2*, Fang Hao1*, Xinlei Yao1, Ye Qiu1, Lei Liu2, Shuyue Wang2, Chunlei Yu1, Zhenbo Song2, Yongli Bao1, Jingwen Yi2, Yanxin Huang1, Yin Wu1, Lihua Zheng1, Ying Sun2, Guannan Wang1, Xiaoguang Yang1,3, Shaonian Yang1,4, Luguo Sun1✉, Yuxin Li2✉

1. National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, China
2. Research Center of Agriculture and Medicine gene Engineering of Ministry of Education, Northeast Normal University, Changchun 130024, China
3. School of Physics, Northeast Normal University, Changchun 130024, China
4. The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
* Co-first author

✉ Corresponding authors: Email: sunlg388edu.cn (Luguo Sun), liyx486edu.cn (Yuxin Li). Tel: 86-0431-8916-5922; Fax: 86-0431-8916-5917.

Citation:
Liang C, Hao F, Yao X, Qiu Y, Liu L, Wang S, Yu C, Song Z, Bao Y, Yi J, Huang Y, Wu Y, Zheng L, Sun Y, Wang G, Yang X, Yang S, Sun L, Li Y. Hypericin maintians PDX1 expression via the Erk pathway and protects islet β-cells against glucotoxicity and lipotoxicity. Int J Biol Sci 2019; 15(7):1472-1487. doi:10.7150/ijbs.33817. https://www.ijbs.com/v15p1472.htm
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Abstract

Graphic abstract

A decrease in islet β-cell mass is closely associated with the development and progression of diabetes. Therefore, protection against β-cell loss is an essential measure to prevent and treat diabetes. In this study, we investigated the protective effects of non-photoactivated hypericin, a natural compound, on β-cells both in vitro and in vivo. In vitro, hypericin greatly improved INS-1 cell viability under high-glucose and high-fatty-acid conditions by inhibiting glucotoxicity- and lipotoxicity-induced apoptosis and nitric oxide (NO) production. Then, we further demonstrated that hypericin elicited its protective effects against glucotoxicity and lipotoxicity in INS-1 cells by attenuating the reduction in pancreatic duodenal homeobox-1 (PDX1) expression and Erk activity. In vivo, prophylactic or therapeutic use of hypericin inhibited islet β-cell apoptosis and enhanced the anti-oxidative ability of pancreatic tissue in high-fat/high-sucrose (HFHS)-fed mice, thus alleviating β-cell loss and maintaining or improving β-cell mass and islet size. More importantly, hypericin treatment decreased fasting blood glucose, improved glucose intolerance and insulin intolerance, and alleviated hyperinsulinaemia in HFHS-fed mice. Therefore, hypericin showed preventive and therapeutic effects against HFHS-induced onset of type II diabetes in mice. Hypericin possesses great potential for development as an anti-diabetes drug in the future.

Keywords: Hypericin, β-cell protection, apoptosis, diabetes

Citation styles

APA
Liang, C., Hao, F., Yao, X., Qiu, Y., Liu, L., Wang, S., Yu, C., Song, Z., Bao, Y., Yi, J., Huang, Y., Wu, Y., Zheng, L., Sun, Y., Wang, G., Yang, X., Yang, S., Sun, L., Li, Y. (2019). Hypericin maintians PDX1 expression via the Erk pathway and protects islet β-cells against glucotoxicity and lipotoxicity. International Journal of Biological Sciences, 15(7), 1472-1487. https://doi.org/10.7150/ijbs.33817.

ACS
Liang, C.; Hao, F.; Yao, X.; Qiu, Y.; Liu, L.; Wang, S.; Yu, C.; Song, Z.; Bao, Y.; Yi, J.; Huang, Y.; Wu, Y.; Zheng, L.; Sun, Y.; Wang, G.; Yang, X.; Yang, S.; Sun, L.; Li, Y. Hypericin maintians PDX1 expression via the Erk pathway and protects islet β-cells against glucotoxicity and lipotoxicity. Int. J. Biol. Sci. 2019, 15 (7), 1472-1487. DOI: 10.7150/ijbs.33817.

NLM
Liang C, Hao F, Yao X, Qiu Y, Liu L, Wang S, Yu C, Song Z, Bao Y, Yi J, Huang Y, Wu Y, Zheng L, Sun Y, Wang G, Yang X, Yang S, Sun L, Li Y. Hypericin maintians PDX1 expression via the Erk pathway and protects islet β-cells against glucotoxicity and lipotoxicity. Int J Biol Sci 2019; 15(7):1472-1487. doi:10.7150/ijbs.33817. https://www.ijbs.com/v15p1472.htm

CSE
Liang C, Hao F, Yao X, Qiu Y, Liu L, Wang S, Yu C, Song Z, Bao Y, Yi J, Huang Y, Wu Y, Zheng L, Sun Y, Wang G, Yang X, Yang S, Sun L, Li Y. 2019. Hypericin maintians PDX1 expression via the Erk pathway and protects islet β-cells against glucotoxicity and lipotoxicity. Int J Biol Sci. 15(7):1472-1487.

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