Differential Equations Seminar: Janita Patwardhan
UMBC
Monday, October 21, 2019 · 11 AM - 12 PM
Title: Flipping the Switch: Islet desynchronization through cell silencing
Abstract: Pancreatic β cells, responsible for secreting insulin into the bloodstream and maintaining glucose homeostasis, are organized in the islets of Langerhans as clusters of electrically coupled cells. Gap junctions, connecting neighboring cells, coordinate the behavior of the islet, leading to synchronized oscillations in electrical activity in healthy patients. Recent experimental work has shown that silencing special hub cells can lead to a disruption in the synchronous behavior, calling into question the democratic paradigm of islet insulin secretion with more or less equal input from each β cell. A mechanistic model representing the electrical and calcium dynamics of β cells during insulin secretion was applied to a network of cells (nodes) and gap junctions (edges) with the desire of replicating this hub cell hypothesis. Functional connectivity networks were built from the simulated calcium traces, with some networks classified as scale-free, confirming experimental results. Potential hub cells were identified using centrality measures, but their silencing was unable to desynchronize the islet. Instead, switch cells that can turn off the activity of the islet were found by systemically silencing each cell in the network. These cells either are highly active instigators of islet activity or are essential for calcium wave propagation, neighboring highly active clusters of cells. The results presented will work towards clearly defining and disproving the hub cell hypothesis.