Aggregation of islet amyloid polypeptide (IAPP) into islet amyloid results in β-cell toxicity in human type 2 diabetes. To determine the effect of islet amyloid formation on gene expression, we performed ribonucleic acid (RNA) sequencing (RNA-seq) analysis using cultured islets from either wild-type mice (mIAPP), which are not amyloid prone, or mice that express human IAPP (hIAPP), which develop amyloid. Comparing mIAPP and hIAPP islets, 5025 genes were differentially regulated (2439 upregulated and 2586 downregulated). When considering gene sets (reactomes), 248 and 52 pathways were up- and downregulated, respectively. Of the top 100 genes upregulated under two conditions of amyloid formation, seven were common. Of these seven genes, only steroidogenic acute regulatory protein (Star) demonstrated no effect of glucose per se to modify its expression. We confirmed this differential gene expression using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and also demonstrated the presence of STAR protein in islets containing amyloid. Furthermore, Star is a part of reactomes representing metabolism, metabolism of lipids, metabolism of steroid hormones, metabolism of steroids and pregnenolone biosynthesis. Thus, examining gene expression that is differentially regulated by islet amyloid has the ability to identify new molecules involved in islet physiology and pathology applicable to type 2 diabetes.

中文翻译：

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胰岛淀粉样蛋白形成的基于RNA-seq的恒星上调识别。

胰岛淀粉样蛋白多肽（IAPP）聚集为胰岛淀粉样蛋白会导致人2型糖尿病的β细胞毒性。为了确定胰岛淀粉样蛋白形成对基因表达的影响，我们使用来自非淀粉样蛋白倾向的野生型小鼠（mIAPP）或表达人的小鼠的培养胰岛进行了核糖核酸（RNA）测序（RNA-seq）分析IAPP（hIAPP），可产生淀粉样蛋白。比较mIAPP和hIAPP胰岛，差异调节了5025个基因（上调2439个，下调2586个）。考虑基因组（反应基因组）时，分别有248条和52条通路被上调和下调。在两种淀粉样蛋白形成条件下上调的前100个基因中，有七个是常见的。在这七个基因中 只有类固醇生成的急性调节蛋白（Star）本身没有表现出葡萄糖改变其表达的作用。我们使用定量逆转录聚合酶链反应（qRT-PCR）确认了这种差异基因表达，并且还证明了在含有淀粉样蛋白的胰岛中存在STAR蛋白。此外，Star是代表代谢，脂质代谢，类固醇激素代谢，类固醇代谢和孕烯醇酮生物合成的反应组的一部分。因此，检查受胰岛淀粉样蛋白差异调节的基因表达具有鉴定与适用于2型糖尿病的胰岛生理学和病理学有关的新分子的能力。我们使用定量逆转录聚合酶链反应（qRT-PCR）确认了这种差异基因表达，并且还证明了在含有淀粉样蛋白的胰岛中存在STAR蛋白。此外，Star是代表代谢，脂质代谢，类固醇激素代谢，类固醇代谢和孕烯醇酮合成的反应组的一部分。因此，检查受胰岛淀粉样蛋白差异调节的基因表达具有鉴定与适用于2型糖尿病的胰岛生理学和病理学有关的新分子的能力。我们使用定量逆转录聚合酶链反应（qRT-PCR）确认了这种差异基因表达，并且还证明了在含有淀粉样蛋白的胰岛中存在STAR蛋白。此外，Star是代表代谢，脂质代谢，类固醇激素代谢，类固醇代谢和孕烯醇酮合成的反应组的一部分。因此，检查受胰岛淀粉样蛋白差异调节的基因表达具有鉴定与适用于2型糖尿病的胰岛生理学和病理学有关的新分子的能力。