首页> 外文期刊>Cellular Physiology and Biochemistry >Decreasing Txnip mRNA and Protein Levels in Pancreatic MIN6 Cells Reduces Reactive Oxygen Species and Restores Glucose Regulated Insulin Secretion
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Decreasing Txnip mRNA and Protein Levels in Pancreatic MIN6 Cells Reduces Reactive Oxygen Species and Restores Glucose Regulated Insulin Secretion

机译:胰腺MIN6细胞中Txnip mRNA和蛋白水平的降低减少了活性氧的种类并恢复了葡萄糖调节的胰岛素分泌

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Background and aims Recently, thioredoxin-interacting protein (Txnip) expression has been implicated in a number of cellular events associated with diabetes, with increased Txnip levels associated with reduced glucose uptake into peripheral tissues, increased reactive oxygen species (ROS) in endothelial cells, beta cell glucotoxicity and apoptosis. The potential relevance of Txnip with regards to glucose-regulated insulin secretion (GSIS), a fundamentally important characteristic of beta cells and insulin-producing cells being considered as a possible cell therapy for diabetes, has not yet been investigated. Methods Here, studying glucose-responsive MIN6 B1(GSIS) and cells which had significantly reduced response to glucose after time in culture i.e. MIN6 B1(Non-GSIS), using ELISAs; qRT-PCR; immunoprecipitation and Western blotting; transient and stable (siRNA/shRNA and cDNA) approaches to achieve Txnip knock-down or over-expression, respectively,we established a direct association between Txnip expression and GSIS. Results Specifically, increasing Txnip levels correlate with increased intracellular ROS levels and with significant GSIS loss.Conversely, both transient and stable knock-down of Txnip expression was associated with GSIS recovery. Conclusion This, we believe, is another reason in favour of targeting Txnip as a novel approach for diabetes-related therapy.
机译:背景和目的最近,硫氧还蛋白相互作用蛋白(Txnip)的表达与许多与糖尿病有关的细胞事件有关,其中Txnip的水平升高与外周组织中葡萄糖的摄取减少,内皮细胞的活性氧(ROS)升高, β细胞的糖毒性和凋亡。尚未研究Txnip与葡萄糖调节的胰岛素分泌(GSIS)的潜在相关性,后者是β细胞和胰岛素产生细胞的根本重要特征,被认为是糖尿病的一种可能的细胞疗法。方法在这里,使用ELISA研究葡萄糖反应性MIN6 B1(GSIS)和培养后经过一段时间后对葡萄糖反应显着降低的细胞,即MIN6 B1(Non-GSIS)。定量RT-PCR免疫沉淀和蛋白质印迹瞬时和稳定(siRNA / shRNA和cDNA)方法分别实现Txnip敲低或过表达,我们在Txnip表达和GSIS之间建立了直接联系。结果特别是,Txnip水平的升高与细胞内ROS水平的升高和GSIS的显着降低有关。相反,Txnip表达的瞬时和稳定敲低与GSIS的恢复相关。结论我们认为,这是支持将Txnip靶向作为糖尿病相关治疗的一种新方法的另一个原因。

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