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: 7673563
• 负责人: Xiaoqing Tang
• 金额: $ 10.37万
• 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 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7673563
• 关键词: Adipocytes; Aftercare; Application procedure; Beta Cell; Cardiovascular Diseases; Cell Line; Cell physiology; Cells; Development; Diabetes Mellitus; Disease; Down-Regulation; Gene Expression; Gene Silencing; Genetic Transcription; Glucose; Goals; Insulin; Laboratories; Lead; Membrane; MicroRNAs; Microarray Analysis; Molecular Profiling; Mus; Non-Insulin-Dependent Diabetes Mellitus; Oligonucleotides; Physiological; Play; Population; Production; 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; endocrine pancreas development; glucose transport; insight; insulin secretion; insulinoma; islet; novel; novel therapeutic intervention; overexpression; 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）：