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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8
Fiscal Year
2016
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U.S. National Inst Diabetes/Digst/Kidney
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Striegel, Deborah A; Hara, Manami; Periwal, Vipul (2016) Adaptation of pancreatic islet cyto-architecture during development. Phys Biol 13:025004
Striegel, Deborah A; Hara, Manami; Periwal, Vipul (2015) The Beta Cell in Its Cluster: Stochastic Graphs of Beta Cell Connectivity in the Islets of Langerhans. PLoS Comput Biol 11:e1004423
Poudel, Ananta; Savari, Omid; Striegel, Deborah A et al. (2015) Beta-cell destruction and preservation in childhood and adult onset type 1 diabetes. Endocrine 49:693-702
Grapov, Dmitry; Fahrmann, Johannes; Hwang, Jessica et al. (2015) Diabetes Associated Metabolomic Perturbations in NOD Mice. Metabolomics 11:425-437
Hoang, Danh-Tai; Matsunari, Hitomi; Nagaya, Masaki et al. (2014) A conserved rule for pancreatic islet organization. PLoS One 9:e110384
Jo, Junghyo; Hörnblad, Andreas; Kilimnik, German et al. (2013) The fractal spatial distribution of pancreatic islets in three dimensions: a self-avoiding growth model. Phys Biol 10:036009
Wang, Xiaojun; Misawa, Ryosuke; Zielinski, Mark C et al. (2013) Regional differences in islet distribution in the human pancreas--preferential beta-cell loss in the head region in patients with type 2 diabetes. PLoS One 8:e67454
Kilimnik, German; Jo, Junghyo; Periwal, Vipul et al. (2012) Quantification of islet size and architecture. Islets 4:167-72
Jo, Junghyo; Hara, Manami; Ahlgren, Ulf et al. (2012) Mathematical models of pancreatic islet size distributions. Islets 4:
Jo, Junghyo; Kilimnik, German; Kim, Abraham et al. (2011) Formation of pancreatic islets involves coordinated expansion of small islets and fission of large interconnected islet-like structures. Biophys J 101:565-74

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