Novel aspects of the molecular mechanisms controlling insulin secretion
Open accessAbstract
Pancreatic β‐cells secrete insulin by Ca 2+‐dependent exocytosis of secretory granules. β‐cell exocytosis involves SNARE (soluble NSF‐attachment protein receptor) proteins similar to those controlling neurotransmitter release and depends on the close association of L‐type Ca 2+ channels and granules. In most cases, the secretory granules fuse individually but there is ultrastructural and biophysical evidence of multivesicular exocytosis. Estimates of the secretory rate in β‐cells in intact islets indicate a release rate of ∼15 granules per β‐cell per second, 100‐fold higher than that observed in biochemical assays. Single‐vesicle capacitance measurements reveal that the diameter of the fusion pore connecting the granule lumen with the exterior is ∼1.4 nm. This is considerably smaller than the size of insulin and membrane fusion is therefore not obligatorily associated with release of the cargo, a feature that may contribute to the different rates of secretion detected by the biochemical and biophysical measurements. However, small molecules like ATP and GABA, which are stored together with insulin in the granules, are small enough to be released via the narrow fusion pore, which accordingly functions as a molecular sieve. We finally consider the possibility that defective fusion pore expansion accounts for the decrease in insulin secretion observed in pathophysiological states including long‐term exposure to lipids.
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Ca2+ influx through voltage-gated Ca2+ channels is essential for insulin exocytosis.
“This is because Ca2+ influx through voltage-gated Ca2+ channels is essential for insulin exocytosis (169).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [169]
Cites
Dynamics of Insulin Secretion by the Perfused Rat Pancreas
CURRY, D. L., BENNETT, L. L., & GRODSKY, G. M. (1968) · Endocrinology · doi:10.1210/endo-83-3-572 · Cited by 601 · see citing works
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“Interestingly, the complements of the voltage-gated ion channels are quite different in mouse and human β-cells (Braun et al. 2008).”
BackgroundSelf-citationFast insulin secretion reflects exocytosis of docked granules in mouse pancreatic B-cells
Olofsson, C. S., Göpel, S. O., Barg, S., Galvanovskis, J., Ma, X., Salehi, A., Rorsman, P., & Eliasson, L. (2002) · Pflügers Archiv · doi:10.1007/s00424-002-0781-5 · Cited by 290 · see citing works
Self-citationImaging analysis reveals mechanistic differences between first- and second-phase insulin exocytosis
Ohara-Imaizumi, M., Fujiwara, T., Nakamichi, Y., Okamura, T., Akimoto, Y., Kawai, J., Matsushima, S., Kawakami, H., Watanabe, T., Akagawa, K., et al. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200608132 · Cited by 211 · see citing works
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Self-citationRegulated Exocytosis of GABA-containing Synaptic-like Microvesicles in Pancreatic β-cells
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Voltage-Gated Calcium Channels
Catterall, W. A. (2011) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a003947 · Cited by 1,628 · see citing works
Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men
Rorsman, P., & Ashcroft, F. M. (2018) · Physiological Reviews · doi:10.1152/physrev.00008.2017 · Cited by 793 · see citing works
Self-citationThe New Biology and Pharmacology of Glucagon
Müller, T. D., Finan, B., Clemmensen, C., DiMarchi, R. D., & Tschöp, M. H. (2017) · Physiological Reviews · doi:10.1152/physrev.00025.2016 · Cited by 419 · see citing works
Mitochondrial signals drive insulin secretion in the pancreatic β-cell
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Islet cholesterol accumulation due to loss of ABCA1 leads to impaired exocytosis of insulin granules
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A computational systems analysis of factors regulating α cell glucagon secretion
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- Authors
- Eliasson, L., Abdulkader, F., Braun, M., Galvanovskis, J., Hoppa, M. B., & Rorsman, P.
- Affiliations
- Lund University (SE)
- Universidade de São Paulo (BR)
- Churchill Hospital (GB)
- Corresponding author
- Rorsman, Patrik
- Venue
- The Journal of Physiology
- Publisher
- Wiley
- Published
- 2008-07-14
- Volume
- 586
- Issue
- 14
- Pages
- 3313-3324
- ISSN
- 0022-3751 (ISSN-L)
- 1469-7793
- PMC
- PMC2538808
- OpenAlex
- W1894763407
- Cited by
- 198
- References
- 6
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 9 · 2023: 3 · 2022: 13 · 2021: 7 · 2020: 3 · 2019: 3 · 2018: 1 · 2017: 11 · 2016: 10 · 2015: 8 · 2014: 23 · 2013: 11 · 2012: 26
- FWCI
- 3.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Wellcome Trust
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- insulin secretion, pancreatic beta cells, exocytosis, secretory granules, SNARE proteins, L-type calcium channels, fusion pore, ATP release, GABA release, islets
- MeSH terms
- Insulin Secretion, Animals, Calcium, Exocytosis, Insulin, Insulin-Secreting Cells, Mice
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