Journal
BIOPHYSICAL JOURNAL
Volume 110, Issue 3, Pages 733-742Publisher
CELL PRESS
DOI: 10.1016/j.bpj.2015.11.3526
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Funding
- National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [R01-DK46409, K01-DK101683]
- Intramural Research Program of the National Institutes of Health (National Institute of Diabetes and Digestive and Kidney Diseases)
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Pancreatic islets respond to elevated blood glucose by secreting pulses of insulin that parallel oscillations in beta-cell metabolism, intracellular Ca2+ concentration, and bursting electrical activity. The mechanisms that maintain an oscillatory response are not fully understood, yet several models have been proposed. Only some can account for experiments supporting that metabolism is intrinsically oscillatory in beta-cells. The dual oscillator model (DOM) implicates glycolysis as the source of oscillatory metabolism. In the companion article, we use recently developed biosensors to confirm that glycolysis is oscillatory and further elucidate the coordination of metabolic and electrical signals in the insulin secretory pathway. In this report, we modify the DOM by incorporating an established link between metabolism and intracellular Ca2+ to reconcile model predictions with experimental observations from the companion article. With modification, we maintain the distinguishing feature of the DOM, oscillatory glycolysis, but introduce the ability of Ca2+ influx to reshape glycolytic oscillations by promoting glycolytic efflux. We use the modified model to explain measurements from the companion article and from previously published experiments with islets.
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