Human Pancreas Analysis Program-T2D

2型糖尿病（T2 D）是由胰岛素抵抗、肝葡萄糖升高 生产，和受损的胰岛功能，这可能是一个关键的决定因素， 发展起来的然而，负责胰岛功能障碍的分子机制是 不完全定义和大部分未知。为了应对这些挑战，我们提出 响应FOA-DK-18-016，2型人胰腺分析程序的应用 糖尿病（HPAP-T2 D）。我们的合作和跨学科团队将询问T2 D人类 胰腺组织和胰岛从临床表型或“分期”供体使用的范围 RFA中概述的实验方法和新的实验技术。我们的团队将： (1)收集和处理来自以下个体的胰腺和胰岛：（a）前驱糖尿病，（B）T2 D 仅用饮食和/或口服药物治疗的糖尿病，（c）用胰岛素治疗的T2 D糖尿病， 和（d）正常对照，并确定其T2 D的遗传风险;（2）使用广泛的 RFA所要求的分子技术，以及与新的和新兴的 实验方法，以全面表型胰岛分离自 指定供体组，以了解T2 D的分子变化;（3）使用最先进的 结合新的尖端多路复用技术，全面分析 来自指定供体的细胞和细胞外区室中的胰腺组织结构 （4）将这些研究的数据整合到全面的，开放获取的，可搜索的 PANC-DB数据库，并帮助开发此资源，为科学家社区服务 对了解T2 D中的人类胰腺和胰岛生物学感兴趣;（5）创建，增强， 并利用与HPAP-T1 D、HIRN、IIDP、nPOD等互补项目的合作关系， AMP-T2 D和QUOD.我们的研究小组一直在广泛合作研究 人胰腺和胰岛，包括T2 D胰腺器官， 本RFA中要求的信息。我们致力于协调、整合和合作， 从不同的方法与我们的努力的最终输出数据登记是一个 通过PANC-DB向所有对T2 D感兴趣的研究者提供全面的T2 D特征。 因此，我们提出的方案的成功形成应导致更好的理解， T2 D发病机制以及能够预防和/或 逆转紊乱

Type 2 diabetes mellitus (T2D) results from insulin resistance, increased hepatic glucose production, and impaired islet function which is likely a key determinant of whether T2D develops. However, the molecular mechanisms responsible for islet dysfunction are incompletely defined and largely unknown. To address these challenges, we submit this application in response to FOA-DK-18-016, Human Pancreas Analysis Program for Type-2 Diabetes (HPAP-T2D). Our collaborative and interdisciplinary team will interrogate T2D human pancreatic tissue and islets from clinically phenotyped or “staged” donors using the range of experimental approaches outlined in the RFA and new experimental techniques. Our team will: (1) Collect and process the pancreas and islets from individuals with; (a) prediabetes, (b) T2D diabetes treated with only diet and/or oral medications, (c) T2D diabetes treated with insulin, and (d) from normal controls, and determine their genetic risk for T2D; (2) Use the broad range of molecular techniques requested by the RFA and integration with new and emerging experimental approaches to comprehensively phenotype the pancreatic islets isolated from designated donor groups to understand molecular changes in T2D; (3) Use state-of-the-art approaches coupled with new cutting-edge multiplexing technology, to comprehensively analyze pancreatic tissue architecture in cellular and extracellular compartments from designated donor groups; (4) Integrate data from these studies into the comprehensive, open-access, searchable PANC-DB database, and help develop this resource to serve the community of scientists interested in understanding human pancreatic and islet biology in T2D; (5) Create, enhance, and leverage partnerships with complementary programs like HPAP-T1D, HIRN, IIDP, nPOD, AMP-T2D, and QUOD. Our group of investigators has been collaborating extensively on studies of the human pancreas and islets, including T2D pancreatic organs with associated clinical information as called for in this RFA. We are committed to harmonization, integration, and co- registration of data from the different approaches with the ultimate output of our efforts being a comprehensive T2D profile available to all investigators interested in T2D through PANC-DB. Thus, the successful formation of our proposed program should lead to improved understanding of the T2D pathogenesis as well as the design of therapies capable of preventing and/or reversing the disorder.