Here come the newcomer granules, better late than never
Abstract
Exocytosis in pancreatic β-cells employs Munc18/soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes that mediate the priming and docking onto the plasma membrane (PM) of insulin granules, called predocked granules, that sit on the PM until Ca(2+) influx evokes fusion. This accounts for most of the initial peak secretory response. However, the subsequent sustained phase of glucose-stimulated insulin secretion arises from newcomer granules that have a minimal residence time at the PM before fusion. In this Opinion I discuss recent work that has begun to decipher the components of the exocytotic machinery of newcomer granules, including a Munc18/SNARE complex that is different from that mediating the fusion of predocked granules and which can potentially rescue defective insulin secretion in diabetes. These insights are applicable to other neuroendocrine cells that exhibit sustained secretion.
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All the essential proteins required for synaptic vesicle release are also expressed in the β-cell and presumably fulfill the same function(s).
“All the essential proteins required for synaptic vesicle release are also expressed in the β-cell and presumably fulfill the same function(s) (193, 336, 364).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [193]
Cites
Pharmacology, physiology, and mechanisms of incretin hormone action.
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Imaging analysis reveals mechanistic differences between first- and second-phase insulin exocytosis
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The R-SNARE Endobrevin/VAMP-8 Mediates Homotypic Fusion of Early Endosomes and Late Endosomes
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Dual Role of VAMP8 in Regulating Insulin Exocytosis and Islet β Cell Growth
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Self-citationZhu, D., Koo, E., Kwan, E., Kang, Y., Park, S., Xie, H., Sugita, S., & Gaisano, H. Y. (2013) · Diabetologia · doi:10.1007/s00125-012-2757-0 · Cited by 81 · see citing works
Self-citationMunc18b Is a Major Mediator of Insulin Exocytosis in Rat Pancreatic β-Cells
Lam, P. P. L., Ohno, M., Dolai, S., He, Y., Qin, T., Liang, T., Zhu, D., Kang, Y., Liu, Y., Kauppi, M., et al. (2013) · Diabetes · doi:10.2337/db12-1380 · Cited by 44 · 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
Synaptotagmin-7 Functions to Replenish Insulin Granules for Exocytosis in Human Islet β-Cells
Dolai, S., Xie, L., Zhu, D., Liang, T., Qin, T., Xie, H., Kang, Y., Chapman, E. R., & Gaisano, H. Y. (2016) · Diabetes · doi:10.2337/db15-1436 · Cited by 55 · see citing works
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- Authors
- Gaisano, H. Y.
- Affiliations
- University of Toronto (CA)
- Corresponding author
- Gaisano, Herbert Y.
- ORCID
- Gaisano, Herbert Y.
- Venue
- Trends in Endocrinology & Metabolism
- Publisher
- Elsevier BV
- Published
- 2014-08
- Volume
- 25
- Issue
- 8
- Pages
- 381-388
- ISSN
- 1043-2760 (ISSN-L)
- OpenAlex
- W1977303460
- Cited by
- 53
- References
- 7
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 1 · 2023: 3 · 2022: 3 · 2021: 5 · 2020: 6 · 2019: 2 · 2018: 3 · 2017: 9 · 2016: 4 · 2015: 8 · 2014: 2
- FWCI
- 0.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research (MOP69083, MOP86544)
- 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 › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- exocytosis, pancreatic beta cells, insulin secretion, Munc18, SNARE complex, insulin granules, glucose-stimulated insulin secretion, diabetes mellitus, neuroendocrine cells, calcium influx
- MeSH terms
- Biological Transport, Exocytosis, Humans, Insulin, Insulin-Secreting Cells, SNARE Proteins
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