Role of microRNAs in insulin production and secretion in pancreatic beta-cells

microRNA 在胰腺 β 细胞胰岛素产生和分泌中的作用

• 批准号: 7494462
• 负责人: Xiaoqing Tang
• 金额: $ 10.15万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-10 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7494462
• 关键词: Adipocytes; Aftercare; Application procedure; Beta Cell; Cardiovascular Diseases; Cell Line; Cell physiology; Cells; Condition; Development; Diabetes Mellitus; Disease; Down-Regulation; Gene Expression; Gene Silencing; Genetic Transcription; Glucose; Goals; Insulin; Islets of Langerhans; Laboratories; Lead; Membrane; MicroRNAs; Microarray Analysis; Molecular Profiling; Mus; Non-Insulin-Dependent Diabetes Mellitus; Oligonucleotides; Physiological; Play; Population; Production; Protein Overexpression; RNA; RNA Interference; Rattus; Regulation; Research; Research Personnel; Role; Small RNA; Structure of beta Cell of islet; Technology; Therapeutic; Tissues; Training; blood glucose regulation; cancer cell; career; cohort; glucose transport; insight; insulin secretion; insulinoma; islet; novel; novel therapeutics; prevent; response

DESCRIPTION (provided by applicant): The candidate has been previously studying the mechanisms of insulin-regulated glucose transport in 3T3-L1 adipocytes using RNAi technology and later focused on the mechanisms of RNAi and profiling of microRNAs in cancer cells and mouse tissues. To continue her training in the field of diabetes, she has recently joined Dr. Sabire Ozcan's laboratory. Dr. Ozcan's research focuses mainly on glucose-regulated insulin gene transcription in pancreatic beta-cells. The immediate career goal of the candidate is to better acquaint herself with experimental procedures and applications in the regulation of insulin gene expression and glucose regulation of pancreatic beta-cell function. This training will allow her to pursue her long-term goal, which is to study the role of miRNAs in regulating beta-cell function and to elucidate the role of miRNAs in the development of type-ll diabetes, as an independent investigator. Recent studies indicate that a novel population of cellular small RNAs, termed microRNAs (miRNAs), may play an important role in the development of type 2 diabetes. The expression of these miRNAs may be highly regulated under various environmental and physiological conditions; dysregulation of these small RNAs may lead to the development of type 2 diabetes. For example, miR-375 has been discovered to be specifically expressed in pancreatic beta cells and be important in insulin secretion. The functions of most miRNAs in beta cells await to be investigated. The hypothesis of the P.I. is that miRNAs are not functioning alone, but rather, multiple miRNAs act in cohort to regulate beta cell development and insulin production and secretion in response to glucose. The specific aims of this project are: (1) To profile miRNA expression in pancreatic beta cells, in order to identify novel cell-specific and glucose-regulated miRNAs with a recently developed rational miRNA microarray technology; (2) To study the function of the identified glucose-regulated and beta cell-specific miRNAs in MIN6 cells by transfecting with synthetic miRNAs to study overexpression effects and with 2-O-methyl RNA antagomirs to investigate the effects associated with their down-regulation. The results obtained from the proposed activities may lead to the discovery of novel miRNAs or new roles of miRNA network in the development of type 2 diabetes and potential therapeutic approaches to treat or prevent this disease.

描述（由申请人提供）： 该候选人之前一直使用 RNAi 技术研究 3T3-L1 脂肪细胞中胰岛素调节的葡萄糖转运机制，后来重点研究癌细胞和小鼠组织中的 RNAi 机制和 microRNA 分析。为了继续接受糖尿病领域的培训，她最近加入了 Sabire Ozcan 博士的实验室。 Ozcan 博士的研究主要集中在胰腺 β 细胞中葡萄糖调节的胰岛素基因转录。候选人的近期职业目标是更好地熟悉胰岛素基因表达调节和胰腺β细胞功能葡萄糖调节的实验程序和应用。这次培训将使她能够追求自己的长期目标，即作为一名独立研究者，研究 miRNA 在调节 β 细胞功能中的作用，并阐明 miRNA 在 ll 型糖尿病发展中的作用。 最近的研究表明，一种新的细胞小 RNA 群体，称为 microRNA (miRNA)，可能在 2 型糖尿病的发展中发挥重要作用。这些miRNA的表达可能在各种环境和生理条件下受到高度调控；这些小 RNA 的失调可能导致 2 型糖尿病的发生。例如，已发现 miR-375 在胰腺 β 细胞中特异性表达，并且对胰岛素分泌很重要。大多数 miRNA 在 β 细胞中的功能有待研究。 P.I. 的假设重要的是，miRNA 并不是单独发挥作用，而是多个 miRNA 协同作用，调节 β 细胞的发育以及胰岛素的产生和分泌，以响应葡萄糖。该项目的具体目标是：（1）分析胰腺β细胞中的miRNA表达，以便利用最近开发的合理miRNA微阵列技术来识别新型细胞特异性和葡萄糖调节的miRNA； (2) 通过转染合成 miRNA 来研究过表达效应，并转染 2-O-甲基 RNA 拮抗剂来研究与其下调相关的效应，以研究 MIN6 细胞中已鉴定的葡萄糖调节和 β 细胞特异性 miRNA 的功能。从拟议活动中获得的结果可能会导致发现新的 miRNA 或 miRNA 网络在 2 型糖尿病发展中的新作用以及治疗或预防该疾病的潜在治疗方法。