Gap junctions and other mechanisms of cell–cell communication regulate basal insulin secretion in the pancreatic islet
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Non‐Technical Summary The islet of Langerhans secretes the hormone insulin in response to elevated glucose. Interactions between cells within the islet is important for the regulation of insulin secretion, to both suppress basal insulin secretion and enhance the glucose‐stimulated response. We show that multiple mechanisms of cell–cell communication are required for the suppression of basal insulin release. First, gap junctions suppress spontaneous calcium signals which suppresses triggering of insulin release. Second, other juxtacrine mechanisms, regulated by cAMP and glucose, suppress more distal steps in the regulation of insulin granule exocytosis. Each mechanism is sufficiently robust to compensate for a loss of the other and still fully suppress basal insulin release. This new insight into the function of islet of Langerhans is important for understanding the development and treatment of diabetes.
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- Authors
- Benninger, R. K. P., Head, W. S., Zhang, M., Satin, L. S., & Piston, D. W.
- Affiliations
- Vanderbilt University (US)
- Virginia Commonwealth University (US)
- University of Michigan (US)
- Corresponding author
- Benninger, R. K. P.
- Venue
- The Journal of Physiology
- Publisher
- Wiley
- Published
- 2011-11
- Volume
- 589
- Issue
- 22
- Pages
- 5453-5466
- ISSN
- 0022-3751 (ISSN-L)
- 1469-7793
- PMC
- PMC3240884
- OpenAlex
- W1528873260
- Cited by
- 165
- References
- 37
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 11 · 2023: 18 · 2022: 13 · 2021: 20 · 2020: 12 · 2019: 12 · 2018: 4 · 2017: 11 · 2016: 8 · 2015: 9 · 2014: 16 · 2013: 13 · 2012: 8
- FWCI
- 12.10
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- Funders
- U.S. Department of Defense
- Vanderbilt University Medical Center (DK20593, DK58404, CA68485)
- National Institutes of Health (5p60dk020593-31, CA68485, DK 20593, DK-58404)
- National Cancer Institute (CA68485, P30CA068485)
- National Institute of General Medical Sciences (P20GM072048)
- National Institute of Diabetes and Digestive and Kidney Diseases (P60-DK020593, DK-58404, DK 20593, K99DK085145, R01DK053434, R00DK085145, R01DK046409, P30DK058404, P30DK020593, R01 DK 46409)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Keywords
- gap junctions, intercellular communication, basal insulin secretion, pancreatic islets, Cx36, pancreatic beta cells, calcium oscillations, ATP-sensitive potassium channels, cyclic AMP, protein kinase A, juxtacrine signaling, exocytosis, glucose regulation, islet heterogeneity
- MeSH terms
- Insulin Secretion, Gap Junction delta-2 Protein, Cyclic AMP, Animals, Calcium, Cell Communication, Cells, Cultured, Glucose, Insulin, Islets of Langerhans, Membrane Potentials, Gap Junctions, Connexins, Cyclic AMP-Dependent Protein Kinases, Mice, Knockout, Insulin-Secreting Cells, Mice, In Vitro Techniques
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