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Transitions between bursting modes in the integrated oscillator model for pancreatic β-cells.

Authors:
Isabella Marinelli Theodore Vo Luca Gerardo-Giorda Richard Bertram

J Theor Biol 2018 10 20;454:310-319. Epub 2018 Jun 20.

Department of Mathematics and Programs in Neuroscience and Molecular Biophysics, Florida State University, Tallahassee, FL, USA. Electronic address:

Insulin-secreting β-cells of pancreatic islets of Langerhans produce bursts of electrical impulses, resulting in intracellular Ca oscillations and pulsatile insulin secretion. The mechanism for this bursting activity has been the focus of mathematical modeling for more than three decades, and as new data are acquired old models are modified and new models are developed. Comprehensive models must now account for the various modes of bursting observed in islet β-cells, which include fast bursting, slow bursting, and compound bursting. One such model is the Integrated Oscillator Model (IOM), in which β-cell electrical activity, intracellular Ca, and glucose metabolism interact via numerous feedforward and feedback pathways. These interactions can produce metabolic oscillations with a sawtooth time course or a pulsatile time course, reflecting very different oscillation mechanisms. In this report, we determine conditions favorable to one form of oscillations or the other, and examine the transitions between modes of bursting and the relationship of the transitions to the patterns of metabolic oscillations. Importantly, this work clarifies what can be expected in experimental measurements of β-cell oscillatory activity, and suggests pathways through which oscillations of one type can be converted to oscillations of another type.

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http://dx.doi.org/10.1016/j.jtbi.2018.06.017DOI Listing
October 2018

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