Interaction of Glycolysis and Mitochondrial Respiration in Metabolic Oscillations of Pancreatic Islets

Authors

Richard Bertram, Florida State UniversityFollow
Leslie S. Satin, Virginia Commonwealth University
Morten Gram Pedersen, Technical University of Denmark
Dan S. Luciani, University of British Columbia
Arthur Sherman, National Institutes of Health

Document Type

Article

Original Publication Date

2007

Journal/Book/Conference Title

The Biophysical Journal

Volume

92

Issue

5

First Page

1544

Last Page

1555

DOI of Original Publication

10.1529/biophysj.106.097154

Comments

Originally published at http://dx.doi.org/10.1529/biophysj.106.097154

Under an Elsevier user license

Date of Submission

February 2015

Abstract

Abstract

Insulin secretion from pancreatic β-cells is oscillatory, with a typical period of 2–7 min, reflecting oscillations in membrane potential and the cytosolic Ca²⁺ concentration. Our central hypothesis is that the slow 2–7 min oscillations are due to glycolytic oscillations, whereas faster oscillations that are superimposed are due to Ca²⁺ feedback onto metabolism or ion channels. We extend a previous mathematical model based on this hypothesis to include a more detailed description of mitochondrial metabolism. We demonstrate that this model can account for typical oscillatory patterns of membrane potential and Ca²⁺ concentration in islets. It also accounts for temporal data on oxygen consumption in islets. A recent challenge to the notion that glycolytic oscillations drive slow Ca²⁺ oscillations in islets are data showing that oscillations in Ca²⁺, mitochondrial oxygen consumption, and NAD(P)H levels are all terminated by membrane hyperpolarization. We demonstrate that these data are in fact compatible with a model in which glycolytic oscillations are the key player in rhythmic islet activity. Finally, we use the model to address the recent finding that the activity of islets from some mice is uniformly fast, whereas that from islets of other mice is slow. We propose a mechanism for this dichotomy.

Rights

From The Biophysical Journal, Bertram, R., Satin, L.S., Pedersen, M.G., et al., Interaction of Glycolysis and Mitochondrial Respiration in Metabolic Oscillations of Pancreatic Islets, Vol. 92, Page 1544. Copyright © 2007 The Biophysical Society. Published by Elsevier Inc. Reprinted with permission.

Is Part Of

VCU Pharmacology and Toxicology Publications