Mangiferin prevents glucolipotoxicity-induced pancreatic beta-cell injury through modulation of autophagy via AMPK-mTOR signaling pathway

The aim of this study was to investigate the protective effects of Mangiferin (MG) on glucolipotoxicity-induced pancreatic beta-cell injury. In vivo administration of MG significantly reduced the level of blood glucose in high-fat diet (HFD)-fed mice. MG treatment inhibited beta-cell Apoptosis in HFD-treated mice. In vitro, MG protected INS-1 cells against Apoptosis and impairment of Insulin secretion following High glucose/Palmitic acid (HG/PA) treatment. MG treatment enhanced Autophagy flux which was blocked by HG/PA treatment. Inhibition of autophagosome formation by 3-Methyladenine or blockade of autolysosome by Chloroquine reversed the protective effects of MG on INS-1 cells. MG treatment increased AMPK phosphorylation and reduced mTOR activation in INS-1 cells. Administration of the AMPK blocker abrogated MG-induced Autophagy, and similar results were observed in INS-1 cells after cotreatment with MG and mTOR Activator. In conclusion, MG ameliorated pancreatic beta-cell injury induced by glucolipotoxicity through modulation of Autophagy via the AMPK-mTOR pathway.

AMPK; Mangiferin; autophagy; glucolipotoxicity; pancreatic beta-cell.