The pancreatic islet is a complex tissue consisting of multiple endocrine cell types, capillaries, and a peri-islet basement membrane. The 3D organization of cells, blood vessels, and basement membrane (BM), enhances islet function by (1) supporting beta cell electrochemical coupling and synchronization through gap junctions between adjacent cells and (2) providing access to nutrients and signals for beta cell survival and function through contact with capillaries and BM. Though a quantitative understanding of islet structure is lacking, there is strong evidence linking islet structural changes to diabetes progression. Studies of these changes in islet structure will enhance understanding of diabetes-related losses in islet function and lead to the development of new therapeutics for diabetic and prediabetic patients. Here, we have quantified healthy adult islet tissue structure through a single-cell analysis of the cell-cell and cell-BM interactions at individual endocrine cell plasma membranes. We have used this single-cell data to identify endocrine cell subtypes, as defined by cell morphology and structural niche. We have also identified spatially-defined clusters of beta cells through a graph analysis of cell-cell connectivity. We report a baseline quantification of structure for healthy adult human and mouse islets. These data both provide an answer to the ongoing debate regarding the differences in structure between human and mouse islets and set the stage for future quantification of islet structure in diabetes.
O.A. Creasey: None. J.B. Sneddon: Advisory Panel; Self; Encellin. Advisory Panel; Spouse/Partner; Encellin. Z.J. Gartner: None.
National Science Foundation (1650113, DBI-1548297); National Institutes of Health (P30DK063720); Chan-Zuckerberg Biohub; Bakar Foundation