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Team 4 – Investigating How Calcium Diffusion Affects Metabolic Oscillations and Synchronization of Pancreatic Beta Cells

Team Members: George Eskander1, Jennifer Houser2, Ellen Prochaska3, and Jessica Wojtkiewicz4
Graduate Assistant: Teresa Lebair5
Faculty Mentor: Bradford E. Peercy5
Clients: Margaret Watts6 and Arthur Sherman6

1Department of Computer Science and Electrical Engineering, University of Maryland, Baltimore County,
2Department of Mathematics and Statistics, East Tennessee State University,
3Department of Mathematics, Creighton University,
4Department of Mathematics, Louisiana State University,
5Department of Mathematics and Statistics, University of Maryland, Baltimore County,
6Laboratory of Biological Modeling, National Institutes of Health

Team4All

About the Team

Our team, George Eskandar, Jennifer Houser, Ellen Prochaska, and Jessica Wojtkiewicz, participated in the REU Site: Interdisciplinary Program in High Performance Computing located in the Department of Mathematics and Statistics at UMBC. Our project focused on investigating how calcium diffusion affects metabolic oscillations and synchronization of pancreatic beta cells. Through the assistance of our faculty mentor, Dr. Bradford E. Peercy from the Department of Mathematics and Statistics at UMBC, our graduate research assistant, Teresa Lebair also from the Department of Mathematics and Statistics at UMBC, and our clients, Dr. Arthur Sherman and Dr. Margaret Watts from the Laboratory of Biological Modeling at NIH, our team was able to use the Dual Oscillator Model given to us by Dr. Sherman and Dr. Watts in order to simulate pancreatic islet behavior.

Problem Introduction

In order to further understand diabetes mellitus, it is necessary to investigate the dynamics of insulin secretion into the bloodstream. Beta cell clusters called islets of Langerhans located in the pancreas are responsible for the production and regulation of insulin based on changes in glucose and calcium concentration levels. Using the Dual Oscillator Model (DOM), we examined how calcium handling within individual pancreatic beta cells affects the synchronization of oscillations within electrically coupled cells.

Dual Oscillator Model

We utilized a revised version of the DOM provided by Dr. Watts and Dr. Sherman to study the effects of calcium diffusion between beta cells. The model is separated into three components: electrical, glycolytic, and mitochondrial. The DOM consists of seven differential equations and seven independent variables that represent membrane potential, calcium concentration and various metabolite concentrations.

Figure1

Figure 1: Schematic showing how the electrical, glycolytic, and mitochondrial components interact with one another to form the DOM.

Oscillation Results

Using our Matlab code, we produced plots that show the effect of calcium diffusion in a 3x3x3 islet with initial conditions drawn from a normal distribution with 20 percent standard deviation. When voltage coupling was low, calcium diffusion played a role in the synchronization of the metabolic oscillations over a span of 30 minutes; however, when voltage coupling was high, there was little variation when the calcium diffusion was also added.

Figure2

Figure 2: Plot showing the voltage, calcium, and FBP traces for voltage coupling = 0 pS and calcium diffusion = 0 / ms

Figure3

Figure 3: Plot showing the voltage, calcium, and FBP traces for voltage coupling = 10 pS and calcium diffusion = 0 / ms

Figure4

Figure 4: Plot showing the voltage, calcium, and FBP traces for voltage coupling = 10 pS and calcium diffusion = 1 / ms

Islet Synchronization

Using the Pearson correlation (Matlab corr function) and the minimum row mean, we measured the synchronization of pancreatic islets with various voltage coupling and calcium diffusion parameters.

Figure5

Figure 5: Plot showing scaled image data from a 2-D matrix containing synchronization indices for pancreatic islets with corresponding voltage coupling and calcium diffusion parameters
(yellow – high synchronization, blue – low synchronization).

Conclusions

Through the DOM, we were able to conclude that calcium diffusion between beta cells in a pancreatic islet does indeed synchronize metabolic oscillations when voltage coupling is low (e.g., 1, 5, 10 pS); when voltage coupling is high (approximately 50 pS), the role of calcium in the synchronization of metabolic oscillations is overshadowed by voltage coupling. Ultimately, calcium diffusion between pancreatic beta cells plays a role in the synchronization of metabolic oscillations.

 

Links

George Eskander, Jennifer Houser, Ellen Prochaska, Jessica Wojtkiewicz, Teresa Lebair, Bradford E. Peercy, Margaret Watts, and Arthur Sherman. Investigating how calcium diffusion affects metabolic oscillations and synchronization of pancreatic beta cells. Technical Report HPCF-2015-24, UMBC High Performance Computing Facility, University of Maryland, Baltimore County, 2015. (HPCF machines used: maya.). Reprint in HPCF publications list

Poster presented at the Summer Undergraduate Research Fest (SURF)

Click here to view Team 1’s project
Click here to view Team 2’s project
Click here to view Team 3’s project
Click here to view Team 5’s project
Click here to view Team 6’s project
Click here to view Team 7’s project
Click here to view Team 8’s project