Cyanidin-3-rutinoside Protects INS-1 Pancreatic Β Cells Against High Glucose-Induced Glucotoxicity by Apoptosis

Exposure to high levels of glucose may cause glucotoxicity, leading to pancreatic beta cell dysfunction, including cell apoptosis and impaired glucose-stimulated insulin secretion. The aim of this study was to explore the effect of cyanidin-3-rutinoside (C3R), a derivative of anthocyanin, on glucotoxicity-induced apoptosis in INS-1 pancreatic beta cells. Glucose (30 mM) treatment induced INS-1 pancreatic beta cell death, but glucotoxicity and apoptosis significantly decreased in cells treated with 50 mu M C3R compared to that observed in 30 mM glucose-treated cells. Furthermore, hyperglycemia increased intracellular reactive oxygen species (ROS), lipid peroxidation, and nitric oxide (NO) levels, while C3R treatment reduced these in a dose-dependent manner. C3R also increased the activity of antioxidant enzymes, markedly reduced the expression of pro-apoptotic proteins (such as Bax, cytochrome c, caspase 9, and caspase 3), and increased the expression of the anti-apoptotic protein, Bcl-2, in hyperglycemia-exposed cells. Finally, cell death was examined using annexin V/propidium iodide staining, which revealed that C3R significantly reduced high glucose-induced apoptosis. In conclusion, C3R may have therapeutic effects against hyperglycemia-induced beta cell damage in diabetes.