title: Calcium and Metabolic Oscillations in Pancreatic Islets: Who's Driving the Bus?*
abstract: Pancreatic islets exhibit bursting oscillations in response to elevated blood glucose. These oscillations are accompanied by oscillations in the free cytosolic Ca2+concentration (Cac), which drives pulses of insulin secretion. Both islet Ca2+and metabolism oscillate, but there is some debate about their interrelationship. Recent experimental data show that metabolic oscillations in some cases persist after the addition of diazoxide (Dz), which opens K(ATP) channels, hyperpolarizingβ-cells and preventing Ca2+entry and Ca2+oscillations. Further, in some islets in which metabolic oscillations were eliminated with Dz, increasing the cytosolic Ca2+concentration by the addition of KCl could restart the metabolic oscillations. Here we address why metabolic oscillations persist in some islets but not others, and why raisingCacrestarts oscillations in some islets but not others. We answer these questions using the dual oscillator model (DOM) for pancreatic islets. The DOM can reproduce the experimental data and shows that the model supports two different mechanisms for slow metabolic oscillations, one that requires calcium oscillations and one that does not.
authors.affiliation: National Institutes of Health, Bethesda, MD 20892. The first and sixth authors' research was supported by the NIH/NIDDK Intramural Research Program.
authors.forename: Margaret
authors.initials: M
authors.lastname: Watts
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724. This author's research was supported by the Simons Foundation and the Starr Cancer Consortium (I3-A123).
authors.forename: Bernard
authors.initials: B
authors.lastname: Fendler
authors.affiliation: University of Michigan, Ann Arbor, MI 48105. The third author's research was supported by the National Institutes of Health (F32-DK085960), and the fourth author's research was supported by the National Institutes of Health (R01-DK46409).
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Merrins
authors.affiliation: University of Michigan, Ann Arbor, MI 48105. The third author's research was supported by the National Institutes of Health (F32-DK085960), and the fourth author's research was supported by the National Institutes of Health (R01-DK46409).
authors.forename: Leslie S
authors.initials: LS
authors.lastname: Satin
authors.affiliation: Department of Mathematics and Programs in Neuroscience and Molecular Biophysics, Florida State University, Tallahassee, FL 32306. This author's research was supported by the National Institutes of Health (DK080714).
authors.forename: Richard
authors.initials: R
authors.lastname: Bertram
authors.affiliation: National Institutes of Health, Bethesda, MD 20892. The first and sixth authors' research was supported by the NIH/NIDDK Intramural Research Program.
authors.forename: Arthur
authors.initials: A
authors.lastname: Sherman
keywords: calcium; dual oscillator model; metabolic; oscillations; pancreatic β-cells