Interaction of glycolysis and mitochondrial respiration in metabolic oscillations of pancreatic islets

¹ Florida State University
² Virginia Commonwealth University
³ Technical University of Denmark
⁴ University of British Columbia
⁵ National Institutes of Health

^* To whom correspondence should be addressed. E-mail: bertram{at}sb.fsu.edu.

Submitted on September 11, 2006
Revised on October 10, 2006
Accepted on 28 November 2006

	Abstract

Insulin secretion from pancreatic -cells is oscillatory, with a typical period of 2-7 minutes, 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, while 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, while that from islets of other mice is slow. We propose a mechanism for this dichotomy.

Key Words: bursting, insulin, islet, mathematical model, metabolic oscillations

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