Author: Morten Gram Pedersen, Department of Physics, Technical University of Denmark.
Names and affiliation of other authors:
Richard Bertram, Florida State University, USA;
Dan S. Lucianin, University of British Colombia, Canada;
Arthur Sherman, National Institutes of Health, USA.
Oral or poster: Oral presentation
The beta-cells secrete insulin in response to a glucose stimulus, which starts a series of signaling events of which metabolism of glucose in the glycolytic pathway and the mitochondria, bursting electrical behavior and calcium influx play crucial roles. Moreover, all these events show complex oscillating behavior due to feedback mechanisms.
We have constructed a simple model of mitochondrial metabolism and ATP production. This model is coupled to models of glycolysis, calcium handling and the electrical properties of the plasma membrane.
We demonstrate how the mitochondrial variables are affected by glycolytic products and by Ca2+, and compare the model time courses with experimental time courses of various mitochondrial variables. In particular, we have found that slow oscillations in NAD(P)H lead slow oscillations in Ca2+, supporting the hypothesis that metabolic oscillations drive Ca2+ oscillations rather than vice versa. Nonetheless, we illustrate that in our model membrane hyperpolarization can terminate metabolic oscillations, as has been shown previously by measuring the extracellular oxygen level and is shown here by measuring NAD(P)H.