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Biophys. J. BioFAST: First Published June 30, 2006. doi:10.1529/biophysj.106.087296
© 2006 by the Biophysical Society.

A more recent version of this article appeared on September 15, 2006.
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BIOPHYSICAL THEORY AND MODELING

Glucose modulates [Ca2+]i oscillations in pancreatic islets via ionic and glycolytic mechanisms

Craig S. Nunemaker 1, Richard Bertram 2, Arthur Sherman 3, Krasimira Tsaneva-Atanasova 3, Camille R. Daniel 3 and Leslie S. Satin 4*

1 University of Virginia
2 Florida State University
3 National Institutes of Health
4 Virginia Commonwealth University

* To whom correspondence should be addressed. E-mail: lsatin{at}vcu.edu.

Submitted on April 17, 2006
Revised on May 22, 2006
Accepted on 8 June 2006


  Abstract
Pancreatic islets of Langerhans display complex intracellular calcium changes in response to glucose that include fast (seconds), slow (~5 min), and mixed fast/slow oscillations; the slow and mixed oscillations are likely responsible for the pulses of plasma insulin observed in vivo. To better understand the mechanisms underlying these diverse patterns, we systematically analyzed the effects of glucose on period, amplitude, and plateau fraction (the fraction of time spent in the active phase) of the various regimes of calcium oscillations. We found that in both fast and slow islets, increasing glucose had limited effects on amplitude and period, but increased plateau fraction. In some islets, however, glucose caused a major shift in the amplitude and period of oscillations, which we attribute to a conversion between ionic and glycolytic modes ('regime change'). Raising glucose increased the plateau fraction equally in fast, slow, and regime changing islets. A mathematical model of the pancreatic islet consisting of an ionic subsystem interacting with a slower metabolic oscillatory subsystem (Bertr am et al., Biophys J. 87:3074) can account for these complex islet calcium oscillations by modifying the relative contributions of oscillatory metabolism and oscillatory ionic mechanisms to electrical activity, with coupling occurring via KATP channels.

Key Words: calcium oscillations, glucose homeostasis, mathematical modeling, metabolism




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Copyright © 2006 by the Biophysical Society.