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、肝脏血糖升高引起 以及胰岛功能受损，这可能是T2D是否存在的关键决定因素 发展起来。然而，导致胰岛功能障碍的分子机制是 不完全定义的，很大程度上未知的。为了应对这些挑战，我们提出如下建议 FOA-DK-18-016人胰腺分析程序在2型中的应用 糖尿病(HPAP-T2D)。我们的协作和跨学科团队将审问T2D人类 来自临床表型或“分期”供者的胰腺组织和胰岛 RFA中概述的实验方法和新的实验技术。我们的团队将： (1)收集和处理患有以下疾病的人的胰腺和胰岛：(A)糖尿病前期，(B)T2D 只用饮食和/或口服药物治疗的糖尿病，(C)用胰岛素治疗的T2D糖尿病， 和(D)正常对照组，并确定他们患T2D的遗传风险；(2)使用广泛的范围 RFA要求的分子技术以及与新出现的技术的整合 分离的胰岛细胞综合表型的实验研究 指定捐赠者群体以了解T2D中的分子变化；(3)使用最先进的 结合新的尖端多路复用技术的方法，以综合分析 指定供体胰腺细胞和细胞外室的胰腺组织构筑 小组；(4)将这些研究的数据纳入全面、开放、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 有兴趣在T2D中了解人类胰腺和胰岛生物学；(5)创造、增强、 并利用与HPAP-T1D、HIRN、IIDP、nPOD、 AMP-T2D和Quod。我们的调查小组一直在广泛合作进行研究 人的胰腺和胰岛，包括与临床相关的T2D胰腺器官 本RFA要求提供的信息。我们致力于协调、整合和共同- 登记来自不同方法的数据，我们努力的最终成果是 所有对T2D感兴趣的研究人员都可以通过PANC-DB获得全面的T2D概况。 因此，我们提议的方案的成功形成应该会带来更好的理解 T2D发病机制以及能够预防和/或 扭转这种混乱局面。