Heterogeneity of the human pancreas

人类胰腺的异质性

基本信息

批准号：
10538549
负责人：
MANAMI HARA
金额：
$ 40.5万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-01-15 至 2024-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10538549
关键词：
3-Dimensional Age Aging Architecture Area Beta Cell Blood capillaries Body mass index Clinical Collection Communities Complex Data Databases Deterioration Development Diabetes Mellitus Disease Extracellular Matrix Foundations Freezing Health Heterogeneity Human Image Analysis Imaging Techniques In Vitro Individual Islets of Langerhans Islets of Langerhans Transplantation Knowledge Measurement Measures Methods Microcirculation Neurons Pancreas Pancreatic duct Paraffin Embedding Patients Pattern Research Research Personnel Research Project Grants Resources Sampling Biases Slice Specimen Stem Cell Research Structure Structure of beta Cell of islet Surface Techniques Thick Three-Dimensional Image Three-Dimensional Imaging Three-dimensional analysis Tissues Transplantation Weight density diabetes pathogenesis diabetic in vivo in vivo imaging individual variation islet nerve supply non-diabetic sex virtual experiments virtual repository

项目摘要

Pancreatic beta-cell mass is a critical determinant of the progression of diabetes. The loss of beta-cells in patients with various types of diabetes has been documented in comparison to age, sex and BMI-matched control subjects. However, the underlying heterogeneity of beta-cell mass in non-diabetic individuals has been less well characterized. We have shown marked intra-individual regional variability in beta-cell/islet mass, which might have confounded accurate measurements of beta-cell mass in past studies due to sampling bias. In this application, we propose to carry out a comprehensive analysis of the whole human pancreas to establish the basic facts about the human pancreas using unbiased quantification methods and importantly in the whole pancreas. Each individual donor pancreas will be analyzed using our large-scale quantification method for beta-cell/islet mass determination in the whole pancreas, which includes mass (i.e. in mg) based on measured pancreas weight/volume and the number of islets per individual. The 3D analyses in the same individual pancreata will provide spatial information about the islets and their microenvironment. This unprecedented depth of analysis of pancreatic islets in the human whole pancreas should advance our understanding of the pathogenesis of diabetes. With the comprehensive analyses of the whole human pancreata described above, we propose to develop “a Virtual Repository Database” that provides systematic data from a large number of whole human pancreata that spans the lifetime to the scientific community.

胰腺β细胞质量是糖尿病进展的关键决定剂。与年龄，性别和BMI匹配的对照受试者相比，已记录了各种类型糖尿病患者的β细胞丧失。然而，非糖尿病个体中β细胞质量的潜在异质性的特征较不那么好。我们已经显示出在β细胞/胰岛质量中明显的个体内区域变异性，由于采样偏差，在过去的研究中可能已经将β细胞质量的准确测量混淆了。在此应用中，我们建议对整个人类胰腺进行全面分析，以使用公正的数量方法来建立有关人胰腺的基本事实，并且在整个胰腺中重要。每个供体胰腺将使用我们的大规模定量方法分析整个胰腺中的β细胞/胰岛质量测定，其中包括基于测量的胰腺重量/体积和每个人的胰岛数量，其中包括质量（即Mg）。同一单个胰腺中的3D分析将提供有关胰岛及其微环境的空间信息。人类全胰腺中胰岛分析的前所未有的深度应提高我们对糖尿病发病机理的理解。通过对上述整个人类胰腺的全面分析，我们建议开发“虚拟存储库数据库”，该数据库提供来自大量整个人类胰腺的系统数据，这些数据跨越了一生，将其跨越科学界。