Changes in the hormone-producing pancreatic islets are central culprits in type 2 diabetes (T2D) pathogenesis. Characterization of gene expression in islets how it is altered in T2D are therefore vital in understanding islet function and T2D pathogenesis. We leveraged RNA-sequencing and genome-wide genotyping in islets from 188 donors to create the Islet Gene View (IGW) platform to make this information easily accessible to the scientific community. The IGW combines expression data for a given gene with phenotypical data such as T2D status, BMI, HbA1c, insulin secretion, purity of islets, etc.), regulation of gene expression by genetic variants e.g., expression quantitative trait loci (eQTLs) and relationship with expression of islet hormones. In IGW, 285 differentially expressed genes (DEGs) were identified in T2D donors islets compared to controls. Forty percent of the DEGs showed cell-type enrichment and a large proportion of them were significantly co-expressed with islet hormone-encoding genes like glucagon (GCG, 56%), amylin (IAPP, 52%), insulin (INS, 44%) and somatostatin (SST,24%). Inhibition of two DEGs, UNC5D and SERPINE2 impaired glucose-stimulated insulin secretion and impacted cell survival in a human beta-cell model.

中文翻译：

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Islet Gene View-促进胰岛研究的工具

产生激素的胰岛的变化是2型糖尿病（T2D）发病机理的罪魁祸首。因此，表征胰岛中基因表达如何在T2D中发生改变对于理解胰岛功能和T2D发病机理至关重要。我们利用来自188个供体的胰岛中的RNA测序和全基因组基因分型，创建了胰岛基因查看（IGW）平台，使科学界可以轻松访问此信息。IGW将给定基因的表达数据与表型数据（例如T2D状态，BMI，HbA1c，胰岛素分泌，胰岛纯度等），遗传变异对基因表达的调控（例如表达定量性状基因座（eQTL）和关系）相结合与胰岛激素的表达。在IGW中，与对照相比，在T2D供体胰岛中鉴定出285个差异表达基因（DEG）。40％的DEGs显示细胞类型富集，其中很大一部分与胰岛激素编码基因如胰高血糖素（GCG，56％），胰岛淀粉样多肽（IAPP，52％），胰岛素（INS，44％）显着共表达。 ）和生长抑素（SST，24％）。在人类β细胞模型中，两种DEG（UNC5D和SERPINE2）的抑制作用会削弱葡萄糖刺激的胰岛素分泌并影响细胞存活。