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Hypericin Protects Islet β-Cells Against Glucotoxicity and Lipotoxicity in Vitro and in Vivo and Prevents the Onset of Diabetes
38 Pages Posted: 5 Oct 2018
More...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 one of the essential ways to prevent or 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 through the inhibition of glucotoxicity- and lipotoxicity-induced apoptosis and nitric oxygen (NO) production. Then, we further demonstrated that hypericin elicited its protective effects on INS-1 cells against glucotoxicity and lipotoxicity by activating Erk signalling and promoting pancreatic duodenal homeobox-1 (PDX1) expression. In vivo, prophylactic use of hypericin inhibited islet β-cell apoptosis and enhanced the anti-oxidative ability of pancreatic tissue in high-fat diet (HFD)-fed mice, thus alleviating β-cell loss and maintaining β-cell mass and islet size. More importantly, prophylactic treatment with hypericin decreased fasting blood glucose, improved glucose intolerance and insulin intolerance, and alleviated hyperinsulinaemia of HFD-fed mice. Therefore, hypericin showed preventive effects against the onset of type II diabetes in mice. Hypericin possesses great potential to be developed as a preventive or therapeutic anti-diabetes drug in the future.
Funding: This work was supported by the National Key New Drug Creation and Manufacturing Program of Ministry of Science and Technology (No. 2013ZX09103003004), the Fundamental Research Funds for the Central Universities (No. 2412018QD011), the Grant of Jilin Province Science & Technology Committee, China (No.20180520105JH, No.20180101242JC; No. 20170414028GH, No. 20150204038YY and No. 20150309003YY), the Grant of Jilin Province Development and Reform Commission, China (No. 2015Y057) and the Grant of Changchun Industry and Information Technology Committee, China (No. 2017(342)).
Declaration of Interest: The authors declare no conflict of interest.
Keywords: Hypericin; β-cell protection; apoptosis; oxidative stress; prevention; diabetes
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