부산대학교 도서관

The islets of Langerhans are critical endocrine micro-organs that secrete hormones regulating energy metabolism in animals. Insulin and glucagon, secreted by beta and alpha cells, respectively, are responsible for metabolic switching between fat and glucose utilization. Dysfunction in their secretion and/or counter-regulatory influence leads to diabetes. Debate in the field centers on the cytoarchitecture of islets, as the signaling that governs hormonal secretion depends on structural and functional factors, including electrical connectivity, innervation, vascularization, and physical proximity. Much effort has therefore been devoted to elucidating which architectural features are significant for function and how derangements in these features are correlated or causative for dysfunction, especially using quantitative network science or graph theory characterizations. Here, we ask if there are non-local features in islet cytoarchitecture, going beyond standard network statistics, that are relevant to islet function. An example is ring structures, or cycles, of α and δ cells surrounding β cell clusters or the opposite, β cells surrounding α and δ cells. These could appear in two-dimensional islet section images if a sphere consisting of one cell type surrounds a cluster of another cell type. To address these issues, we developed two independent computational approaches, geometric and topological, for such characterizations. For the latter, we introduce an application of topological data analysis to determine locations of topological features that are biologically significant. We show that both approaches, applied to a large collection of islet sections, are in complete agreement in the context both of developmental and diabetes-related changes in islet characteristics. The topological approach can be applied to three-dimensional imaging data for islets as well. Author summary: The pancreatic islets or islets of Langerhans are regions of the pancreas that contain endocrine or hormone-producing cells classified as alpha, beta, delta, PP, and epsilon. They are responsible for regulating blood glucose levels, and their dysfunction leads to diabetes. Differences in relative arrangement of alpha, beta, and delta cells has been observed between species. For example, mouse islets predominantly contain beta cells in the central core with alpha and delta cells forming a mantle around them localized in the periphery. Similar arrangement has been seen in small human islets, but larger islets have alpha and delta cells also along the vessels penetrating inside the islet. These findings motivate the debate of the functional significance of these structural patterns. In this work we mathematically define and implement quantitation of ring-structures or cycles of alpha and delta cells around beta cells (and vice versa) using two distinct methods, geometric and topological, in 2D sections of islets. We analyze two different data sets of 2D sections of human islets, one from different developmental stages and another from control and diabetic subjects. Further, we illustrate extension of the topological method to three dimensional data sets. [ABSTRACT FROM AUTHOR]