Molecular mechanisms and regulation of insulin exocytosis as a paradigm of endocrine secretion
Abstract
Secretion of the peptide hormone insulin from pancreatic beta cells constitutes an important step in the regulation of body homeostasis. Insulin is stored in large dense core vesicles and released by exocytosis, a multistage process involving transport of vesicles to the plasma membrane, their docking, priming and finally their fusion with the plasma membrane. Some of the protein components necessary for this process have been identified in beta cells. The export of potent and potentially harmful substances has to be tightly controlled. The secretory response in pancreatic beta cells requires the concerted action of nutrients together with enteric hormones and neurotransmitters acting on G-protein coupled receptors. It is well established that glucose and other metabolizable nutrients depolarize the beta-cell membrane and the ensuing Ca2+ influx through voltage-dependent channels constitutes a main stimulus for insulin exocytosis. Theoretical considerations and recent observations suggest in addition an organizing role for the Ca2+ channel similar to neurotransmission. A second regulatory control on exocytosis is exerted by monomeric and heterotrimeric G-proteins. The monomeric GTPase Rab3A controls insulin secretion through cycling between a guanosine triphosphate liganded vesicle-bound form and a guanosine diphosphate liganded, cytosolic form. The effect of neurohormones is transduced by the heterotrimeric GTPases. Whereas pertussis-toxin sensitive alpha-subunits exert dire…
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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 [364]
The molecular machinery of insulin granule exocytosis bears a strong resemblance to that of synaptic vesicle release at the neuronal synapse.
“The molecular machinery of insulin granule exocytosis bears a strong resemblance to that of synaptic vesicle release at the neuronal synapse (364).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [364]
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Self-citation
- Authors
- Lang, J.
- Affiliations
- University of Geneva (CH)
- Corresponding author
- Lang, Jochen
- ORCID
- Lang, Jochen
- Venue
- European Journal of Biochemistry
- Publisher
- Wiley
- Published
- 1999-01
- Volume
- 259
- Issue
- 1-2
- Pages
- 3-17
- ISSN
- 0014-2956 (ISSN-L)
- 1432-1033
- OpenAlex
- W2049043048
- Cited by
- 347
- References
- 5
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 2 · 2023: 4 · 2022: 7 · 2021: 6 · 2020: 5 · 2019: 3 · 2018: 7 · 2017: 11 · 2016: 7 · 2015: 12 · 2014: 13 · 2013: 14 · 2012: 14
- FWCI
- 5.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- 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 exocytosis, pancreatic beta cells, hormone secretion, dense core vesicles, vesicle docking, vesicle priming, membrane fusion, glucose-stimulated insulin secretion, calcium channels, Rab3A, G proteins, pertussis toxin, Gβγ subunits, neurohormones, G protein-coupled receptors, second messengers
- MeSH terms
- Insulin Secretion, Biological Transport, Carrier Proteins, Endocrine Glands, Exocytosis, Insulin, Islets of Langerhans, Membrane Proteins, Models, Biological, GTP-Binding Proteins, Calcium Signaling
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