Einstein-Mount Sinai Diabetes Research Center

在美国，糖尿病影响着大约3000万人。1型和2型糖尿病最终都是失败的结果 β细胞质量和/或功能。人类的胰岛和β细胞在许多方面与啮齿动物的同类细胞相似 方法不同，但在重要方面也不同。因此，NIDDK、ADA和JDRF正在加大对以下方面的关注 人类β细胞和胰岛生物学的研究。事实上，专注于人类胰岛的研究对于 将啮齿动物胰岛和β细胞的重要发现转化为人类糖尿病的重大进展 研究和治疗。位于西奈山的人类胰岛和腺病毒核心(HIAC)被创造出来 五年前，也支持爱因斯坦-西奈糖尿病研究中心(ES-DRC)的研究基地 作为地区性研究人员，通过特别强调人类小岛，追求小岛生物学。在.期间 在上一个供资周期中，HIAC向50名调查人员提供了专业知识和服务，支持了41份出版物 以及22项联邦和非联邦资助的赠款。因此，我们建议扩大这些受欢迎的 并进一步加强获得和提供与小岛有关的教育、服务和技术，以 纽约市地区的糖尿病研究人员。第一个任务是提供关键的建议、方法、 协助调查人员利用人类小岛进行研究的技术和基础设施，目标是 加深对正常和病理生理胰岛细胞生长和功能的了解。第二项任务是 产生试剂和工具，包括腺病毒或慢病毒，并提供给ES-DRC社区 病毒载体用于基因传递感兴趣的β细胞和其他类型胰岛细胞的cDNA和shRNA以研究β 细胞的再生、分化、存活和功能。这些任务将通过制定 以下具体目标：1)协助新的小岛调查人员进入人类和啮齿动物小岛 和相关细胞系，用于研究人员主导的研究；2)培训学生、博士后研究员、研究人员 和技术人员设计和使用分子、细胞和生理方法来治疗人类和啮齿动物 胰岛生物学和病理生理学；3)提供活的人β细胞的纯群体，使用荧光- 激活细胞分选(FAC)和/或促进特殊方案的使用，腺病毒/慢病毒和 向啮齿动物和人类β细胞和胰岛传递基因的转导方法，以增强研究人员- 启动研究；4)进行专门的胰岛素分泌测定，胰岛生物能学 以及使用同基因、同种异体移植在体外和体内的β细胞分化、增殖、存活和质量 或将啮齿动物/人胰岛移植到免疫受损的正常血糖或糖尿病小鼠模型中；以及 5)协助研究人员进行研究设计和数据解释，以推进有重点的实验方法 1型和2型糖尿病患者胰岛细胞功能和功能障碍的分子和生理学基础。

Diabetes affects some 30 million people in the US. Both Type 1 and Type 2 diabetes ultimately result from failure of beta cell mass and/or function. Human islets and beta cells are similar to their rodent counterparts in many ways, but also differ in important ways. Accordingly, the NIDDK, ADA and JDRF are increasing their focus on research in human beta cell and islet biology. Indeed, research focused on human islets is essential for translating important insights from rodent islets and beta cells into significant advances in human diabetes research and treatment. The Human Islet and Adenovirus Core (HIAC), located at Mount Sinai, was created five years ago to support the research base of the Einstein-Sinai Diabetes Research Center (ES-DRC), as well as regional investigators pursuing islet biology, by providing special emphasis on human islets. During the previous funding cycle, the HIAC provided expertise and services to 50 investigators supporting 41 publications and 22 federally and non-federally funded grants. Consequently, we propose to expand these sought-after services and to further enhance access and availability of islet-relevant education, services and technology to diabetes researchers in the New York City region. The first mission is to provide key advice, methods, technology and infrastructure to assist investigators in the use of human islets for research, with the goal of furthering understanding of normal and pathophysiologic islet cell growth and function. The second mission is to generate, and make available to the ES-DRC community, reagents and tools including adenovirus or lentivirus viral vectors for gene delivery of cDNAs and shRNAs of interest beta cells and other islet cell types to study beta cell regeneration, differentiation, survival and function. These missions will be achieved by developing the following Specific Aims: 1) To assist new islet investigators in obtaining in accessing human and rodent islets and related cell lines for use in investigator-driven studies; 2) To train students, postdoctoral fellows, investigators and technical staff in the design and use of molecular, cellular and physiologic approaches to human and rodent islet biology and pathophysiology; 3) To provide pure populations of live human beta cells using fluorescence- activated cell sorting (FACS) and/or to facilitate the use of specialized protocols, adenovirus/lentivirus and transduction methods for gene delivery to rodent and human beta cells and islets that enhance investigator- initiated research; 4) To conduct specialized assays for the determination of insulin secretion, islet bioenergetics and beta cell differentiation, proliferation, survival and mass in vitro and in vivo using syngeneic, allotransplant or xenotransplant of rodent/human islets into immunocompromised euglycemic or diabetic mouse models; and 5) To assist investigators with study design and data interpretation to advance experimental approaches focused on the molecular and physiologic basis of human islet cell function and dysfunction in Types 1 and 2 diabetes.