RNA Sequencing Facilitates Quantitative Analysis of rat pancreas islet beta cell Transcriptomes in uric acid treat

The effect of uric acid on islet function remains to be confirmed,We applied GSIS, immunofluorescence staining, WB, and flow cytometry to observe the protective effects of uric acid on beta cell apoptosis and insulin deficiency.To further explore the molecular mechanisms involved in this,we found UA could directly suppressed GSIS in both INS-1E cells and primary isolated islets in a dose- and time-dependent manner. RNAseq suggested that CHOP/NLRP3 is critical in the UA-induced beta cell dysfunction. These data suggest that UA might be an independent risk factor for beta cell function which induced beta cell dysfunction via OAT2/chop/ NLRP3 pathway. which provided new insight into the diabetogenic effect of UA.尿酸对胰岛功能的影响仍有待证实。本研究采用葡萄糖刺激胰岛素分泌（Glucose-Stimulated Insulin Secretion, GSIS）实验、免疫荧光染色、蛋白质印迹法（Western Blot, WB）及流式细胞术，观察尿酸对β细胞凋亡及胰岛素分泌不足的保护作用。为进一步探索其潜在分子机制，我们发现尿酸可在INS-1E细胞与原代分离胰岛中以剂量和时间依赖性方式直接抑制GSIS。RNA测序（RNA Sequencing, RNAseq）结果显示，CHOP/NLRP3通路在尿酸诱导的β细胞功能障碍中发挥关键作用。上述数据表明，尿酸或为β细胞功能的独立危险因素，可通过有机阴离子转运体2（Organic Anion Transporter 2, OAT2）/CHOP/NLRP3通路诱导β细胞功能障碍，这为阐明尿酸的致糖尿病效应提供了新的研究视角。