Document Type

Article

Original Publication Date

2004

Journal/Book/Conference Title

The Biophysical Journal

Volume

87

Issue

5

First Page

3074

Last Page

3087

DOI of Original Publication

10.1529/biophysj.104.049262

Comments

Originally published at http://dx.doi.org/10.1529/biophysj.104.049262

Under an Elsevier user license

Date of Submission

February 2015

Abstract

Abstract

Pancreatic islets of Langerhans produce bursts of electrical activity when exposed to stimulatory glucose levels. These bursts often have a regular repeating pattern, with a period of 10–60 s. In some cases, however, the bursts are episodic, clustered into bursts of bursts, which we call compound bursting. Consistent with this are recordings of free Ca2+ concentration, oxygen consumption, mitochondrial membrane potential, and intraislet glucose levels that exhibit very slow oscillations, with faster oscillations superimposed. We describe a new mathematical model of the pancreatic β-cell that can account for these multimodal patterns. The model includes the feedback of cytosolic Ca2+ onto ion channels that can account for bursting, and a metabolic subsystem that is capable of producing slow oscillations driven by oscillations in glycolysis. This slow rhythm is responsible for the slow mode of compound bursting in the model. We also show that it is possible for glycolytic oscillations alone to drive a very slow form of bursting, which we call “glycolytic bursting.” Finally, the model predicts that there is bistability between stationary and oscillatory glycolysis for a range of parameter values. We provide experimental support for this model prediction. Overall, the model can account for a diversity of islet behaviors described in the literature over the past 20 years.

Rights

From The Biophysical Journal, Bertram, R., Satin, L.S., Zhang, M., et al., Calcium and Glycolysis Mediate Multiple Bursting Modes in Pancreatic Islets, Vol. 87, Page 3074. Copyright © 2004 The Biophysical Society. Published by Elsevier Inc. Reprinted with permission.

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VCU Pharmacology and Toxicology Publications

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