Abstract
Recently, the prevalence of diabetes mellitus (DM) in the world continues to rise, which has seriously threatened human health. Enhanced pancreatic β-cell death is one of the important factors in the pathogenesis of type 1 diabetes mellitus (T1DM). Berberine, an alkaloid, plays a series of pharmacological functions in many disease. The purpose of this study was to explore the specific mechanisms of berberine in the high glucose (HG) stimulated pancreatic β-cell. The 30 mM D-glucose stimulated mouse pancreatic β cells (NIT-1) was used to estabilish T1DM model in vitro. Then the cell viability was detected by CCK-8 assay. The lactic dehydrogenase (LDH), reactive oxygen species (ROS), Iron, malondialdehyde (MDA), glutathione (GSH), and glutathione peroxidase 4 (GPX4) levels were determined by corresponding kits. The cell death was evaluated by PI staining. Western blot was performed to measure the O-linked N-acetylglucosamine (O-GlcNAc) and O-GlcNAc transferase (OGT) protein levels. The results showed that berberine treatment significantly increased the cell viability, GPX4 activity and GSH levels, and decreased the ROS, Iron, MDA levels and PI positive cells in the HG stimulated NIT-1 cells. Additionally, the molecular docking analysis showed that berberine could bind to OGT. Berberine treatment significantly decreased the global O-GlcNAc levels and OGT protein expression in the HG stimulated NIT-1 cells. Furthermore, OGT overexpression reversed the role of berberine in the HG stimulated NIT-1 cells. This study demonstrated that berberine treatment inhibited the ferroptosis of pancreatic β-cell under high-glucose condition via decreasing the OGT expressions.