Discovery of microRNA regulatory modules controlling human pancreatic islet funct

标题：发现控制人胰腺的microRNA调控模块 胰岛功能 这项研究项目的目标是全面地描述 MicroRNAs(MiRNAs)在人胰岛功能中的作用胰岛细胞负责 对血糖水平变化的代谢反应。进行性功能障碍 胰岛是2型糖尿病的基础，2型糖尿病是一种以高血糖为特征的慢性疾病， 这可能会导致大量的发病率，包括肾衰竭。基因调控 推动胰岛生物学的网络(GRN)在很大程度上是未知的。MiRNA是POST- 转录调控因子和GRN的关键成分。最近的研究表明 与胰岛功能有关的miRNAs。MiRNA表达的综合分析和 人类初级胰岛的活动将显著增加我们对GRN的了解 这是小岛生物学的基础。因此，该项目将使用高通量基因组 系统研究静息和葡萄糖刺激下所有miRNAs的方法 原生人类胰岛(目标1)，并确定影响其 差异表达模式(目标2)和靶向活性(目标3)。这些目标将 对绘制胰岛GRN作出重大贡献，这将有助于识别 临床相关药理靶点在胰岛病理生理学研究中的应用 糖尿病。

Title: Discovery of microRNA regulatory modules controlling human pancreatic islet function The goal of this research project is to characterize comprehensively the role of microRNAs (miRNAs) in human pancreatic islet function. Islet cells are responsible for the metabolic response to changes in blood glucose levels. Progressive dysfunction of the islet underlies type 2 diabetes, a chronic condition characterized by hyperglycemia, which can lead to substantial morbidity including kidney failure. The gene regulatory networks (GRNs) that drive islet biology are largely uncharacterized. miRNAs are post- transcriptional regulators and critical components of GRNs. Recent studies have implicated miRNAs in islet function. Comprehensive analysis of miRNA expression and activity in primary human islets will significantly increase our knowledge of the GRNs that underlie islet biology. Therefore, this project will use high-throughput genomic approaches to systematically characterize all miRNAs in resting and glucose-stimulated primary human islets (Aim 1), and identify the regulatory modules that influence their differential expression patterns (Aim 2) and targeting activity (Aim 3). These aims will contribute significantly toward mapping islet GRNs, which will facilitate the identification of clinically relevant pharmacological targets for addressing islet pathophysiology in diabetes.