COMPUTER MODELING OF HETEROGENEOUS B-CELL POPULATIONS

Arthur Sherman and Paul Smolen

Mathematical Research Branch
National Institutes of Health
Bethesda, MD 20892

Keywords: bursting, oscillations, glucose-sensing, heterogeneity,
synchronization, cellular communication, gap junctions

Beta-cells differ significantly with respect to their electrical and
secretory properties (Pipeleers, 1992), leading us to consider whether
heterogeneity may have functional significance for the behavior of
beta-cell populations, such as the natural unit, the islet of Langerhans. 
On the other hand, beta-cells in islets behave essentially synchronously,
at least with regard to electrical activity (Eddlestone et al., 1984) and
cytosolic Ca2+ levels (Santos et al., 1991).  Several questions arise: 

How does the islet synchronize?  Are the reported size and density of gap
junctional connections adequate to produce synchrony? 

What is the role of cell heterogeneity?  Is it important for building the
graded response to glucose or merely an obstacle that must be overcome in
order to achieve coordinated behavior? 

Does glucose increase insulin secretion by recruiting more cells
(Pipeleers, 1992)  into activity or by increasing the output of each cell
(Beigelman et al., 1977)?

How is the oscillatory activity of the islet generated in the absence of a
pacemaker? 

We have explored these questions by computer simulations of cell clusters
(ca. 100 -- 1000 cells), each represented by differential equations of the
Chay-Keizer family for ionic channel kinetics and Ca2+ handling.