Insulin granule dynamics in pancreatic beta cells
Open accessAbstract
Glucose-induced insulin secretion in response to a step increase in blood glucose concentrations follows a biphasic time course consisting of a rapid and transient first phase followed by a slowly developing and sustained second phase. Because Type 2 diabetes involves defects of insulin secretion, manifested as a loss of first phase and a reduction of second phase, it is important to understand the cellular mechanisms underlying biphasic insulin secretion. Insulin release involves the packaging of insulin in small (diameter approximately 0.3 micro m) secretory granules, the trafficking of these granules to the plasma membrane, the exocytotic fusion of the granules with the plasma membrane and eventually the retrieval of the secreted membranes by endocytosis. Until recently, studies on insulin secretion have been confined to the appearance of insulin in the extracellular space and the cellular events preceding exocytosis have been inaccessible to more detailed analysis. Evidence from a variety of secretory tissues, including pancreatic islet cells suggests, however, that the secretory granules can be functionally divided into distinct pools that are distinguished by their release competence and/or proximity to the plasma membrane. The introduction of fluorescent proteins that can be targeted to the secretory granules, in combination with the advent of new techniques that allow real-time imaging of granule trafficking in living cells (granule dynamics), has led to an explosion of our knowledge of the pre-exocytotic and post-exocytotic processes in the beta cell. Here we discuss these observations in relation to previous functional and ultra-structural data as well as the secretory defects of Type 2 diabetes.
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Only a small fraction of secretory granules (<1%/h) undergo exocytosis even at high glucose concentrations.
“Only a small fraction of the secretory granules (<1%/h) undergo exocytosis even at high glucose concentrations (571).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [571]
The Ultrastructural correlates of biphasic insulin secretion section (page unavailable) describes sustained glucose-stimulated secretion at 5 granules per minute per beta cell. The same section reports about 10,000 granules per mouse beta cell, making that rate approximately 3% per hour, not less than 1% per hour. (LLM, conf=0.86)
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Experimental — accuracy not yet measuredGranules belonging to the reserve pool have not yet acquired release competence and must undergo a series of ATP-, Ca2+- and temperature-dependent reactions ('mobilization' or 'priming') prior to exocytosis.
“Granules belonging to the reserve pool have not yet acquired release competence and must undergo a series of ATP-, Ca2+- and temperature-dependent reactions (‘mobilization’ or ‘priming’) prior to exocytosis (571).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [571]
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“Finally, we stimulated insulin secretion by 30 mM KCl which causes membrane depolarization, and therefore an increase in intra-cellular Ca 2 + levels by opening voltage-gated channels (Rorsman and Renstr ¨ om, 2003; Hatlapatka et al., 2009).”
- Authors
- Rorsman, P., & Renstr�m, E.
- Affiliations
- Lund University (SE)
- Corresponding author
- Rorsman, P.
- ORCID
- Rorsman, P.
- Venue
- Diabetologia
- Published
- 2003-08-01
- Volume
- 46
- Issue
- 8
- Pages
- 1029-1045
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2105955034
- Cited by
- 844
- References
- 11
- Citations by year
- 2026: 26 · 2025: 33 · 2024: 35 · 2023: 23 · 2022: 29 · 2021: 43 · 2020: 44 · 2019: 39 · 2018: 30 · 2017: 40 · 2016: 41 · 2015: 45 · 2014: 51 · 2013: 38 · 2012: 46
- FWCI
- 5.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Novo Nordisk
- Vetenskapsrådet
- Novo Nordisk Fonden
- 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 › Genetics › Diabetes and associated disorders
- Keywords
- insulin secretion, pancreatic beta cells, secretory granules, granule dynamics, first-phase insulin secretion, second-phase insulin secretion, type 2 diabetes, exocytosis, endocytosis, live-cell imaging, fluorescent protein markers
- MeSH terms
- Insulin Secretion, Animals, Cytoplasmic Granules, Diabetes Mellitus, Endocytosis, Exocytosis, Humans, Insulin, Islets of Langerhans, Models, Biological
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