Yu Chengbi, Qiu Yue, Yan Dongbiao, Zhou Wendi, Wan Jin, Yu Jiewei
Department of Endocrinology, Jiujiang Hospital of Traditional Chinese Medicine, Jiujiang, 332000, China.
Department of Ophthalmology, Jiujiang Hospital of Traditional Chinese Medicine, No.261, South Lushan Road, Jiujiang, 332000, China.
Sci Rep. 2025 May 27;15(1):18504. doi: 10.1038/s41598-025-03537-z.
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.
近年来，全球糖尿病（DM）患病率持续上升，严重威胁人类健康。胰腺β细胞死亡增加是1型糖尿病（T1DM）发病机制的重要因素之一。黄连素是一种生物碱，在多种疾病中发挥一系列药理作用。本研究旨在探讨黄连素在高糖（HG）刺激的胰腺β细胞中的具体作用机制。用30 mM D-葡萄糖刺激小鼠胰腺β细胞（NIT-1）建立体外T1DM模型。然后通过CCK-8法检测细胞活力。用相应试剂盒测定乳酸脱氢酶（LDH）、活性氧（ROS）、铁、丙二醛（MDA）、谷胱甘肽（GSH）和谷胱甘肽过氧化物酶4（GPX4）水平。通过PI染色评估细胞死亡情况。采用蛋白质免疫印迹法检测O-连接的N-乙酰葡糖胺（O-GlcNAc）和O-GlcNAc转移酶（OGT）蛋白水平。结果显示，黄连素处理显著提高了HG刺激的NIT-1细胞的活力、GPX4活性和GSH水平，降低了ROS、铁、MDA水平及PI阳性细胞数量。此外，分子对接分析表明黄连素可与OGT结合。黄连素处理显著降低了HG刺激的NIT-1细胞中的整体O-GlcNAc水平和OGT蛋白表达。此外，OGT过表达逆转了黄连素在HG刺激的NIT-1细胞中的作用。本研究表明，黄连素处理通过降低OGT表达抑制高糖条件下胰腺β细胞的铁死亡。
