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.
Pancreatic beta-cell mass is a critical determinant of the progression of diabetes. However, there is a lack of rigor in understanding the underlying heterogeneity of beta-cell mass in healthy as well as diabetic individuals. We propose to carry out a comprehensive analysis of the whole human pancreas, which will provide a new foundation for pancreatic beta-cell and islet studies in vitro and in vivo by filling a large gap in knowledge about the human pancreas.