Why pancreatic islets burst but single beta cells do not. The heterogeneity hypothesis
Open accessAbstract
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.
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- Authors
- Smolen, P., Rinzel, J., & Sherman, A.
- Affiliations
- National Institutes of Health (US)
- Venue
- Biophysical Journal
- Publisher
- Elsevier BV
- Published
- 1993-06
- Volume
- 64
- Issue
- 6
- Pages
- 1668-1680
- ISSN
- 0006-3495 (ISSN-L)
- PMC
- PMC1262502
- OpenAlex
- W2044121793
- Cited by
- 158
- References
- 33
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 5 · 2022: 3 · 2021: 4 · 2020: 4 · 2019: 6 · 2018: 3 · 2017: 7 · 2016: 7 · 2015: 7 · 2014: 4 · 2013: 4 · 2012: 5
- FWCI
- 5.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biophysical Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
- Keywords
- pancreatic beta cells, beta-cell heterogeneity, electrical coupling, calcium dynamics, glucose detection, synchronization, dose-response relationship
- MeSH terms
- Animals, Cells, Cultured, Electric Conductivity, Glucose, Islets of Langerhans, Mathematics, Membrane Potentials, Models, Biological, Mice
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