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Curcumin attenuates palmitate-induced apoptosis in MIN6 pancreatic β-cells through PI3K/Akt/FoxO1 and mitochondrial survival pathways

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Abstract

Lipotoxicity plays a vital role in development and progression of type 2 diabetes. Prolonged elevation of free fatty acids especially the palmitate leads to pancreatic β-cell dysfunction and apoptosis. Curcumin (diferuloylmethane), a polyphenol from the curry spice turmeric, is considered to be a broadly cytoprotective agent. The present study was designed to determine the protective effect of curcumin on palmitate-induced apoptosis in β-cells and investigate underlying mechanisms. Our results showed that curcumin improved cell viability and enhanced glucose-induced insulin secretory function in MIN6 pancreatic β-cells. Palmitate incubation evoked chromatin condensation, DNA nick end labeling and activation of caspase-3 and -9. Curcumin treatment inhibited palmitate-induced apoptosis, relieved mitochondrial depolarization and up-regulated Bcl-2/Bax ratio. Palmitate induced the generation of reactive oxygen species and inhibited activities of antioxidant enzymes, which could be neutralized by curcumin treatment. Moreover, curcumin could promote rapid phosphorylation of Akt and nuclear exclusion of FoxO1 in MIN6 cells under lipotoxic condition. Phosphatidylinositol 3-kinase and Akt specific inhibitors abolished the anti-lipotoxic effect of curcumin and stimulated FoxO1 nuclear translocation. These findings suggested that curcumin protected MIN6 pancreatic β-Cells against apoptosis through activation of Akt, inhibition of nuclear translocation of FoxO1 and mitochondrial survival pathway.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China No. 81473235, 91129727, 81020108031, 81270049 to X.-J. Li, No. 81373405 and 30901803 to L. Tie, Research Fund from Ministry of Education of China (111 Projects No. B07001), Beijing Higher Education Young Elite Teacher Project (No. YETP0053), Leading Academic Discipline Project of Beijing Education Bureau (No. BMU20110254) and the Fund of Janssen Research Council China (JRCC2011).

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  1. State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing Key Laboratory of Tumor Systems Biology, Peking University, 38 Xueyuan Road, Beijing, 100191, People’s Republic of China

    Feng Hao, Jinsen Kang, Yajun Cao, Shengjun Fan, Haopeng Yang, Yu An, Yan Pan, Lu Tie & Xuejun Li

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  1. Feng Hao
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Hao, F., Kang, J., Cao, Y. et al. Curcumin attenuates palmitate-induced apoptosis in MIN6 pancreatic β-cells through PI3K/Akt/FoxO1 and mitochondrial survival pathways. Apoptosis 20, 1420–1432 (2015). https://doi.org/10.1007/s10495-015-1150-0

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