Kiss-and-run exocytosis and fusion pores of secretory vesicles in human β-cells
Abstract
Exocytosis of secretory vesicles results in the release of insulin from pancreatic beta-cells, although little is known about this process in humans. We examined the exocytosis of single secretory vesicles and their associated fusion pores in human beta-cells by cell-attached capacitance and conductance measurement. Unitary capacitance steps were observed, consistent with the exocytosis of single secretory vesicles. These were often coincident with increases in patch conductance representing the presence of a stable fusion pore. In some events, the fusion pore closed, mediating kiss-and-run, which contributed 20% of the exocytotic events. The cAMP-raising agent forskolin (5 microM) doubled the relative contribution of kiss-and-run. This effect was confirmed visually in MIN6 cells expressing a fluorescent granule probe. Thus, we demonstrate the unitary capacitance steps and fusion pores during single vesicle exocytosis in human beta-cells. Furthermore, these secretory vesicles can undergo rapid recycling by kiss-and-run, and this process is up-regulated by cAMP.
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Studies on human and mouse β-cells have revealed that 80-90% of capacitance steps belong to a single class of events with a mean magnitude of 3-5 fF, as expected for granules with a diameter of 0.3-0.4 μm.
“Studies on human and mouse β-cells (253) have revealed that the 80-90% of capacitance steps belong to a single class of events with a mean magnitude of 3-5 fF, as expected for granules with a diameter of 0.3-0.4 µm.”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [253]
Cites
Voltage‐gated and resting membrane currents recorded from B‐cells in intact mouse pancreatic islets
Göpel, S., Kanno, T., Barg, S., Galvanovskis, J., & Rorsman, P. (1999) · The Journal of Physiology · doi:10.1111/j.1469-7793.1999.00717.x · Cited by 226 · see citing works
Self-citationRegulated Exocytosis of GABA-containing Synaptic-like Microvesicles in Pancreatic β-cells
Braun, M., Wendt, A., Birnir, B., Broman, J., Eliasson, L., Galvanovskis, J., Gromada, J., Mulder, H., & Rorsman, P. (2004) · The Journal of General Physiology · doi:10.1085/jgp.200308966 · Cited by 130 · see citing works
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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-citationRegulation of Insulin Secretion in Human Pancreatic Islets
Rorsman, P., & Braun, M. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-030212-183754 · Cited by 599 · see citing works
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- Authors
- Hanna, S. T., Pigeau, G. M., Galvanovskis, J., Clark, A., Rorsman, P., & MacDonald, P. E.
- Affiliations
- University of Alberta (CA)
- University of Oxford (GB)
- Corresponding author
- MacDonald, Patrick E.
- Venue
- Pflügers Archiv - European Journal of Physiology
- Published
- 2008-09-16
- Volume
- 457
- Issue
- 6
- Pages
- 1343-1350
- ISSN
- 0031-6768 (ISSN-L)
- 1432-2013
- OpenAlex
- W2094982559
- Cited by
- 57
- References
- 2
- Citations by year
- 2023: 1 · 2022: 2 · 2021: 4 · 2020: 3 · 2019: 4 · 2018: 4 · 2017: 7 · 2016: 4 · 2015: 6 · 2013: 5 · 2012: 7
- FWCI
- 1.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Pflügers Archiv - European Journal of Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust (084655)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Keywords
- kiss-and-run exocytosis, fusion pore, secretory vesicles, pancreatic beta cells, insulin secretion, forskolin, cAMP signaling, vesicle recycling, MIN6 cells
- MeSH terms
- Insulin Secretion, Adult, Animals, Exocytosis, Colforsin, Humans, Insulin, Male, Middle Aged, Secretory Vesicles, Electric Capacitance, Insulin-Secreting Cells
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