In T1D, pancreatic islets are infiltrated by lymphocytes (so called “insulitis”) and those T cells appear to drive β-cell dysfunction, and death. However, it has been long observed that not all islets within a T1D donor’s pancreas are infiltrated; even those in close proximity such that some islets have many infiltrating T cells while others appear quite pristine. We do not understand the reason for this heterogeneity. In addition, we do not understand the heterogeneity
of individual islet responses to glucose stimulation.
In this proposal, we will complete the development of a micro-punch that will enable us to ‘punch out’ individual islets from donors of pancreatic slices and characterize their cellular constituents, transcriptional profiles, and function using an in vitro GSIS assay.