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首页> 外文期刊>Cellular Physiology and Biochemistry >NADPH Oxidase 2-derived Reactive Oxygen Species are Involved in Dysfunction and Apoptosis of Pancreatic β-cells Induced by Low Density Lipoprotein
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NADPH Oxidase 2-derived Reactive Oxygen Species are Involved in Dysfunction and Apoptosis of Pancreatic β-cells Induced by Low Density Lipoprotein

机译:NADPH氧化酶2衍生的活性氧物种参与低密度脂蛋白诱导的胰腺β细胞功能异常和凋亡。

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biBackground /i/bIncreased levels of plasma cholesterol are a common feature of patient of type 2 diabetes. However, the links between elevated levels of low-density lipoprotein (LDL) and dysfunction of β-cells are still unclear. biMethods /i/bThe apoEsup-/-/supmice were fed with a high-fat, cholesterol-rich diet for 8 weeks. Blood samples were collected from the mice for measurement of plasma glucose, lipids. The pancreas were embedded in OCT compound and frozen immediately in liquid nitrogen for further analysis. To examine the effects of LDL on β-cell function, insulin content, cell apoptosis and ROS production were measured in pancreatic islets of apoEsup-/-/supmice and mouse pancreatic β–cell line NIT-1. Relative cell signal pathways were determined by Western blot. biResults /i/bDecreased insulin content and increased apoptosis and ROS production were found in pancreatic islets of apoEsup-/-/supmice, accompanied by elevated plasma LDL. The ROS levels were significantly enhanced in NIT-1 cells exposed to LDL. Reduced insulin synthesis and glucose-stimulated insulin secretion and elevated apoptosis were reversed by suppression of NOX2 expression. Moreover, LDL induced dysfunction and apoptosis of pancreatic NIT-1 cells through JNK and p53 pathways, which were rescued by siRNA-mediated NOX2 reduction. biConclusions /i/bNOX2-derived ROS may play a key role in LDL-induced dysfunction and apoptosis of pancreatic β-cells through JNK and p53 pathways.
机译:背景 血浆胆固醇水平升高是2型糖尿病患者的常见特征。但是,低密度脂蛋白(LDL)水平升高与β细胞功能障碍之间的联系仍不清楚。 方法 给apoE -/-小鼠喂食高脂,富含胆固醇的饮食8周。从小鼠收集血液样品以测量血浆葡萄糖,脂质。将胰腺包埋在OCT化合物中,并立即在液氮中冷冻以进行进一步分析。为了检查低密度脂蛋白对β细胞功能的影响,测量了apoE -/-小鼠胰岛和小鼠胰腺β-细胞系NIT-1的胰岛素含量,细胞凋亡和ROS的产生。通过Western印迹确定相对细胞信号途径。 结果 在apoE -/-小鼠的胰岛中发现胰岛素含量降低,细胞凋亡和ROS产生增加,同时血浆LDL升高。在暴露于LDL的NIT-1细胞中,ROS水平显着提高。抑制NOX2表达可逆转胰岛素合成减少,葡萄糖刺激的胰岛素分泌和凋亡增加。此外,LDL通过JNK和p53途径诱导胰腺NIT-1细胞功能异常和凋亡,这通过siRNA介导的NOX2还原得以挽救。 结论 来源于NOX2的ROS可能在LDL诱导的JNK和p53途径的胰腺β细胞功能障碍和细胞凋亡中起关键作用。

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