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Dynamics of Computational Islet Simulations: Islets with majority mutated open KATP channels retain bursting-
Article in a journal
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Area Biomedicine |
Author(s)
Gemma Gearhart
, Shuai Jiang
, Thomas J. May
, Jane Pan
, Samuel Khuyis
, Matthias K. Gobbert
, Bradford E. Peercy
, Arthur Sherman
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Published in
Letters in Biomathematics |
Year 2014 |
Abstract The study of pancreatic beta-cells comprises a crucial part of the study of the group of diseases known as diabetes. These cells exist in groups known as islets of Langerhans and are responsible for storing and producing insulin. They exhibit electrical bursting behavior during insulin production that correlates with the rate at which insulin is secreted into the bloodstream. Coupling is a natural process within islets that enables the cells to communicate with one another and transfer various ions and electrical currents; coupling of both voltage and metabolites can occur. We model multicellular islets using an existing system of seven ordinary differential equations to model beta cell function. We simulate cells with mutated KATp channels that remain open indefinitely, which have been described in experimental studies but not yet modeled. Simulations ran with these mutations reveal the existence of a bursting death threshold, described by the least percentage of cells in the islet that must be mutated for electrical bursts to completely disappear. We determine that this threshold is independent of coupling strengths, cell distribution, and possibly islet dimension; however, we also determined that this threshold is dependent on the glucose influx rate. |
AD Tools ADiMat |
BibTeX
@ARTICLE{
Gearhart2014DoC,
author = "Gemma Gearhart and Shuai Jiang and Thomas J. May and Jane Pan and Samuel Khuyis and
Matthias K. Gobbert and Bradford E. Peercy and Arthur Sherman",
title = "Dynamics of Computational Islet Simulations: {I}slets with majority mutated open
{KATP} channels retain bursting",
journal = "Letters in Biomathematics",
volume = "1",
number = "1",
pages = "3--15",
year = "2014",
doi = "10.1080/23737867.2014.11414466",
url = "http://dx.doi.org/10.1080/23737867.2014.11414466",
abstract = "The study of pancreatic beta-cells comprises a crucial part of the study of the
group of diseases known as diabetes. These cells exist in groups known as islets of Langerhans and
are responsible for storing and producing insulin. They exhibit electrical bursting behavior during
insulin production that correlates with the rate at which insulin is secreted into the bloodstream.
Coupling is a natural process within islets that enables the cells to communicate with one another
and transfer various ions and electrical currents; coupling of both voltage and metabolites can
occur. We model multicellular islets using an existing system of seven ordinary differential
equations to model beta cell function. We simulate cells with mutated KATp channels that remain open
indefinitely, which have been described in experimental studies but not yet modeled. Simulations ran
with these mutations reveal the existence of a bursting death threshold, described by the least
percentage of cells in the islet that must be mutated for electrical bursts to completely disappear.
We determine that this threshold is independent of coupling strengths, cell distribution, and
possibly islet dimension; however, we also determined that this threshold is dependent on the
glucose influx rate.",
ad_area = "Biomedicine",
ad_tools = "ADiMat"
}
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