Human Pancreas Analysis Program-T2D

人类胰腺分析程序-T2D

• 批准号: 10907128
• 负责人: MARK A. ATKINSON
• 金额: $ 35万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10907128
• 关键词: Acceleration; Address; Alberta province; Alpha Cell; Architecture; Atlases; Beta Cell; Biological Assay; Biology; Body Weight decreased; Capital; Cellular biology; Characteristics; Clinical; Collaborations; Color; Communities; Coupled; Data; Databases; Development; Diabetes Mellitus; Diet; Disease; Florida; Fostering; Functional disorder; Genetic Risk; Glucagon; Goals; Hepatic; Heterogeneity; Human; Human BioMolecular Atlas Program; Human Genetics; Hyperglycemia; Impairment; Individual; Infrastructure; Insulin; Insulin Resistance; Insulin-Dependent Diabetes Mellitus; Islets of Langerhans; Knowledge; Leadership; Life; Medicine; Molecular; Molecular Analysis; Molecular Biology; Neonatal; Non-Insulin-Dependent Diabetes Mellitus; Oral; Organ; Organ Donations; Organ Donor; Output; Pancreas; Pathogenesis; Pathology; Pharmaceutical Preparations; Phenotype; Physiology; Positioning Attribute; Prediabetes syndrome; Process; Productivity; Recording of previous events; Research; Research Personnel; Resolution; Resources; Role; Scientist; Site; Techniques; Technology; Tissues; bariatric surgery; biomarker development; clinical development; clinical phenotype; collaborative approach; data integration; design; experience; extracellular; glucose production; improved; insulin secretion; interdisciplinary approach; interest; islet; multimodality; new technology; non-diabetic; prevent; programs; response; targeted treatment; therapeutic development; therapy design

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.

2型糖尿病（T2D）由胰岛素抵抗引起，肝葡萄糖增加 生产和胰岛功能受损，这可能是T2D是否的关键确定器 发展。但是，导致胰岛功能障碍的分子机制是 未完全定义且在很大程度上未知。为了应对这些挑战，我们提出 响应FOA-DK-18-016的应用，类型2的人类胰腺分析计划 糖尿病（HPAP-T2D）。我们的合作和跨学科团队将审问T2D人类 胰腺组织和胰岛来自临床表型或“上演”供体 RFA和新实验技术中概述的实验方法。我们的团队将： （1）从有个人那里收集和处理胰腺和胰岛； （a）糖尿病前，（b）T2D 仅用饮食和/或口服药物治疗的糖尿病，（c）用胰岛素治疗的T2D糖尿病， （d）来自正常对照，并确定其T2D的遗传风险； （2）使用广泛范围 RFA要求的分子技术以及与新的和新兴 实验性的方法，用于全面表型从与从 指定的供体组了解T2D中的分子变化； （3）使用最新的 方法加上新的尖端多路复用技术，以全面分析 指定供体的细胞和细胞外室中的胰组织结构 群体； （4）将这些研究的数据集成到全面的，开放的，可搜索的 PANC-DB数据库，并帮助开发此资源以服务于科学家社区 有兴趣了解T2D中的人类胰腺和胰岛生物学； （5）创建，增强， 并利用与HPAP-T1D，HIRN，IIDP，NPOD， AMP-T2D和QUOD。我们的研究人员一直在研究广泛合作 人类胰腺和胰岛，包括带有相关临床的T2D胰腺器官 在此RFA中要求的信息。我们致力于协调，集成和共同 从不同方法的数据注册，我们努力的最终输出是一个 所有对T2D感兴趣的调查人员都可以通过PANC-DB感兴趣。 这，我们提出的计划的成功形成应提高理解 T2D发病机理以及能够预防和/或的疗法的设计 扭转疾病。