Einstein-Mount Sinai Diabetes Research Center

糖尿病影响着美国约 3000 万人。 1 型和 2 型糖尿病最终都是由于失败造成的 β 细胞质量和/或功能。人类胰岛和 β 细胞在许多方面与啮齿类动物相似 方式，但在重要方面也有所不同。因此，NIDDK、ADA 和 JDRF 正在更加关注 人类β细胞和胰岛生物学研究。事实上，针对人类胰岛的研究对于 将啮齿动物胰岛和β细胞的重要见解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) 诞生 五年前还支持爱因斯坦-西奈糖尿病研究中心（ES-DRC）的研究基地 作为研究胰岛生物学的区域研究人员，特别重视人类胰岛。期间 在上一个资助周期中，HIAC 为 50 名研究人员提供了专业知识和服务，支持 41 种出版物 以及 22 项联邦和非联邦资助的赠款。因此，我们建议扩大这些广受欢迎的 服务，并进一步加强与胰岛相关的教育、服务和技术的获取和利用 纽约地区的糖尿病研究人员。第一个任务是提供关键建议、方法、 协助研究人员利用人类胰岛进行研究的技术和基础设施，其目标是 进一步了解正常和病理生理胰岛细胞的生长和功能。第二个任务是 生成并向 ES-DRC 社区提供包括腺病毒或慢病毒在内的试剂和工具 用于对感兴趣的 β 细胞和其他胰岛细胞类型进行 cDNA 和 shRNA 基因递送以研究 β 的病毒载体 细胞再生、分化、存活和功能。这些使命将通过发展 以下具体目标： 1) 协助新的胰岛研究人员获得进入人类和啮齿动物胰岛的能力 以及用于研究者驱动的研究的相关细胞系； 2）培养学生、博士后、研究者 和技术人员设计和使用针对人类和啮齿动物的分子、细胞和生理方法 胰岛生物学和病理生理学； 3) 使用荧光提供纯的活人 β 细胞群 - 激活细胞分选（FACS）和/或促进使用专门的方案、腺病毒/慢病毒和 将基因传递到啮齿动物和人类β细胞和胰岛的转导方法，可增强研究者的能力 发起研究； 4) 进行胰岛素分泌、胰岛生物能量学测定的专门测定 使用同基因、同种异体移植进行体外和体内β细胞分化、增殖、存活和质量 或将啮齿动物/人类胰岛异种移植到免疫功能低下、血糖正常或糖尿病小鼠模型中；和 5) 协助研究人员进行研究设计和数据解释，以推进重点实验方法 1 型和 2 型糖尿病中人类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.