Discovery of microRNA regulatory modules controlling human pancreatic islet funct

标题：发现控制人类胰腺癌的microRNA调控模块 胰岛功能 本研究项目的目标是全面描述 microRNAs（miRNAs）在人类胰岛功能中的作用。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， 这可导致包括肾衰竭在内的严重发病率。基因调控 驱动胰岛生物学的GRN网络在很大程度上没有特征。miRNAs是后 转录调节因子和GRNs的关键组成部分。最近的研究 与胰岛功能相关的miRNA。miRNA表达的综合分析和 在原代人类胰岛中的活性将显著增加我们对GRNs的了解 是胰岛生物学的基础因此，本项目将使用高通量基因组 系统表征静息和葡萄糖刺激下所有miRNA的方法 原代人胰岛（目标1），并确定影响其功能的调控模块。 差异表达模式（Aim 2）和靶向活性（Aim 3）。这些目标将 显著有助于绘制胰岛GRN，这将有助于识别 临床相关的药理学靶点，用于解决胰岛病理生理学， 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.