Modeling and Analysis of Multimodal Bursting in Pancreatic Beta-Cells

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Bertram9981822 The investigator uses mathematical models to study dynamicaland biophysical mechanisms for the multiple modes of burstingobserved in pancreatic Beta-cells. In pancreatic islets,Beta-cells burst with a period of 10-30 seconds, while isolatedBeta-cells burst with periods of either 2-5 seconds or 1-2minutes. The primary goal of this project is to answer thefollowing questions: (1) How does a single oscillator (theBeta-cell) produce such a wide range of bursting behaviors? (2)What biophysical mechanisms drive the different modes ofbursting? (3) Why does the bursting behavior differ betweenisolated cells and intact islets? To address these questions theinvestigator develops a family of mathematical models thatemploy several slow variables. He studies how well these modelsreproduce key electrophysiological and calcium imaging data fromisolated Beta-cells, cell clusters, and intact islets. Pancreatic Beta-cells are the only cells in the human bodythat secrete insulin, a hormone required by other cells toprocess sugars in the blood. If Beta-cells function improperlythen late-onset diabetes occurs, the most common form ofdiabetes. Insulin is secreted from Beta-cells when the cellsgenerate electrical impulses, so understanding the electricalactivity of Beta-cells is crucial to understanding insulinsecretion. For many years mathematical models have providedinsight into the complex electrical behavior of Beta-cells. Inthe current project, the investigator develops improvedmathematical models to understand how Beta-cells produce patternsof electrical impulses that are key to normal insulin secretion.Only when these normal patterns are understood can abnormalelectrical activity, and abnormal insulin secretion resulting indiabetes, be understood.