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Click to add/remove this article to your list of 'My Favorites' An Integrated Pancreatic Beta-Cell Model for Calcium, Inositol (1,4,5)-trisphosphate and cAMP Dynamics

Abstract Number: 2549-PO


Institutions: Chicago, IL.

Results: Proposed mathematical models of pancreatic beta-cell metabolic and calcium regulation still fall short of a comprehensive explanation of existing data. We have further developed our integrated kinetic model of Ca2+ dynamics in the pancreatic beta-cell by including the control of beta-cell mitochondrial bioenergetics and signaling molecules such as cAMP and inositol (1,4,5)-trisphosphate. We have also updated a previous model of the regulation of ionic currents in the plasma membrane by employing an experimental characterization of the conductance of the Na+/K+-adenosinetriphosphatase and other data. The mitochondrial model interrelates the simplified mitochondrial matrix Ca2+, pyruvate and NADH dynamics models with oxidative phosphorylation and electrical gradients. The general model is described by ordinary differential equations for the time rate of change of cytoplasmic and mitochondrial parameters, integrating plasmalemma and mitochondrial membrane potentials, mitochondrial NADH and Ca2+ concentrations, cytoplasmic Ca2+, Na+, inositol (1,4,5)-trisphosphate and cAMP. The model can reproduce qualitatively and semiquantitatively the oscillated response of Ca2+, in-phase inositol (1,4,5)-trisphosphate and antiphase cAMP oscillations in cytoplasm, oscillations in the respiration rate, mitochondrial NADH and mitochondrial membrane potential variations to changes in glucose delivery and messenger action. The model allows in silico testing of the effects of messengers on cytoplasmic and mitochondrial calcium dynamics in the beta-cell following glucose-stimulation.