Pancreatic islets of Langerhans consist of endocrine cells, primarily alpha, beta and delta cells, which secrete glucagon, insulin, and somatostatin, respectively, to regulate plasma glucose. We have collaborated with the Hara laboratory for a number of years in work aimed at elucidating the structure of islets of Langerhans and how this structure might be altered in diabetes. Beta cells form locally connected clusters within islets that act in concert to secrete insulin upon glucose stimulation. Due to the central functional significance of this local connectivity in the placement of beta cells in an islet, it is important to characterize it quantitatively. Graph theory provides a framework for such a characterization of beta-cell mass, enabling quantification of the cytoarchitecture of the entire beta-cell population in an islet. Using large-scale imaging data for thousands of islets containing hundreds of thousands of cells in human organ donor pancreata, we show that quantitative graph characteristics differ between control and type 2 diabetic islets. We have applied our graph theory of dynamic islet changes to data supplied by Manami Hara on islet structure for a very large number of islets from different ages of development. Using this data, we have found the dynamic rules that govern the observed changes in islet morphology during the course of human development.
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