Why pancreatic islets burst but single beta cells do not. The heterogeneity hypothesis.

Abstract:

:Previous mathematical modeling of beta cell electrical activity has involved single cells or, recently, clusters of identical cells. Here we model clusters of heterogeneous cells that differ in size, channel density, and other parameters. We use gap-junctional electrical coupling, with conductances determined by an experimental histogram. We find that, for reasonable parameter distributions, only a small proportion of isolated beta cells will burst when uncoupled, at any given value of a glucose-sensing parameter. However, a coupled, heterogeneous cluster of such cells, if sufficiently large (approximately 125 cells), will burst synchronously. Small clusters of such cells will burst only with low probability. In large clusters, the dynamics of intracellular calcium compare well with experiments. Also, these clusters possess a dose-response curve of increasing average electrical activity with respect to a glucose-sensing parameter that is sharp when the cluster is coupled, but shallow when the cluster is decoupled into individual cells. This is in agreement with comparative experiments on cells in suspension and islets.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Smolen P,Rinzel J,Sherman A

doi

10.1016/S0006-3495(93)81539-X

subject

Has Abstract

pub_date

1993-06-01 00:00:00

pages

1668-80

issue

6

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(93)81539-X

journal_volume

64

pub_type

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