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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.

胰腺细胞质量是糖尿病进展的关键决定因素。与年龄、性别和bmi匹配的对照组相比，各种类型糖尿病患者的β细胞损失已被记录在案。然而，非糖尿病个体β细胞质量的潜在异质性尚未得到很好的表征。我们已经证明了β细胞/胰岛质量的个体内部区域差异，这可能会由于采样偏差而混淆过去研究中β细胞质量的准确测量。在这个应用中，我们建议对整个人体胰腺进行全面的分析，用无偏量化的方法来建立关于人体胰腺的基本事实，重要的是在整个胰腺。每个个体供体胰腺将使用我们的大规模定量方法进行分析，以确定整个胰腺的β细胞/胰岛质量，其中包括基于测量的胰腺重量/体积和每个个体的胰岛数量的质量（即以毫克为单位）。对同一个体胰岛的三维分析将提供有关胰岛及其微环境的空间信息。这种对人类整个胰腺胰岛的前所未有的深度分析应该促进我们对糖尿病发病机制的理解。在对人类全胰脏进行综合分析的基础上，我们建议建立一个“虚拟胰脏库数据库”，为科学界提供跨越整个生命周期的大量人类全胰脏的系统数据。