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Synchronization and Phase Transitions in the Pancreatic Islet with Implications for Diabetes Ìý

Tom Hraha

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Date and time:Ìý

Thursday, March 13, 2014 - 2:00pm

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ECCR 257

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As science has successfully broken down the elements of many biological systems, the network dynamics of large-scale cellular interactions has emerged as a new frontier. Diabetes, which is of increasing importance with the rise of the Western diet, is commonly caused by a deterioration of these multicellular dynamics in a micro-organ called the islet of Langerhans. The islet exists as a network of heterogeneous coupled oscillators which serves to coordinate synchronized electrical activity and insulin release at high blood glucose levels, and also suppress this activity at basal levels. This prevent hyper- and hypoglycemia, respectively. Despite its importance, how multicellular dynamics coordinate this binary response is not fully understood. Using bond percolation, we show that the islet develops as a random network and that a critical level of nodal coupling is needed to prevent a diabetic-like phenotype. Phase transitions between global active/inactive states were also seen as a function of inactive/contrarian elements, which were induced genetically or pharmacologically. We show that this behavior can also be reproduced using a computational model of islet electrophysiology. This work not only explains how the islet leverages cellular heterogeneity to synchronize behavior, but also sheds new insight into emergent multicellular dynamics, specifically the inhibitory dynamics of coupled networks.