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Biophys J. 2016 Feb 2;110(3):733-742. doi: 10.1016/j.bpj.2015.11.3526.

Ca2+ Effects on ATP Production and Consumption Have Regulatory Roles on Oscillatory Islet Activity.

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Department of Mathematics, Florida State University, Tallahassee, Florida.
Laboratory of Biological Modeling, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
Division of Endocrinology, Diabetes & Metabolism, Department of Medicine and Department of Biomolecular Chemistry, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin; William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin.
Department of Pharmacology and Brehm Diabetes Center, University of Michigan, Ann Arbor, Michigan.
Department of Mathematics, Florida State University, Tallahassee, Florida; Programs in Neuroscience and Molecular Biophysics, Florida State University, Tallahassee, Florida. Electronic address:


Pancreatic islets respond to elevated blood glucose by secreting pulses of insulin that parallel oscillations in β-cell metabolism, intracellular Ca(2+) 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 β-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 Ca(2+) 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 Ca(2+) 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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