Signals and pools underlying biphasic insulin secretion.
Open accessAbstract
Rapid and sustained stimulation of β-cells with glucose induces biphasic insulin secretion. The two phases appear to reflect a characteristic of stimulus-secretion coupling in each β-cell rather than heterogeneity in the time-course of the response between β-cells or islets. There is no evidence indicating that biphasic secretion can be attributed to an intrinsically biphasic metabolic signal. In contrast, the biphasic rise in cytoplasmic Ca2+ concentration ([Ca2+]i) induced by glucose is important to shape the two phases of secretion. The first phase requires a rapid and marked elevation of [Ca2+]i and corresponds to the release of insulin granules from a limited pool. The magnitude of the second phase is determined by the elevation of [Ca2+]i, but its development requires production of another signal. This signal corresponds to the amplifying action of glucose and may serve to replenish the pool of granules that are releasable at the prevailing [Ca2+]i. The species characteristics of biphasic insulin secretion and its perturbations in pathological situations are discussed.
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No depletion of docked granules occurred when islets were depolarized in the presence of glucose.
“Importantly, no depletion of docked granules occurred when islets were depolarized in the presence of glucose.”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [268]
In “Does a change in the [Ca²⁺]i pattern affect the secretory pattern?” (page unavailable), the paper reports that glucose maintained insulin responses during repeated depolarization and suggests that glucose refills a limited releasable granule pool. It does not report measurements of docked granules or establish that no depletion occurred; the responses initially decreased slightly. (LLM, conf=0.82)
Experimental — accuracy not yet measuredWhen glucose is added to islets stimulated by glibenclamide or high [K+]o after insulin secretion has almost declined to basal levels, a secondary slowly developing acceleration of insulin secretion is observed.
“Indeed, when glucose is added to islets stimulated by glibenclamide or high [K+]o after insulin secretion has almost declined to basal levels, a secondary slowly developing acceleration of insulin secretion is observed (Figures 14B and 23C).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [268]
The ‘Perturbations of biphasic insulin secretion’ section says that adding glucose to islets stimulated by high K+ or a sulfonylurea produces a delayed, progressive increase in insulin secretion. A separate passage in ‘Does a change in the [Ca2+]i pattern affect the secretory pattern?’ says high-K+-induced secretion returns almost to basal values. The copy does not specifically name glibenclamide or establish that glucose was added after secretion had nearly returned to basal levels. (LLM, conf=0.82)
Experimental — accuracy not yet measuredInsulin secretion elicited by the combination of high-[K+]o depolarization and glucose exhibits a sustained 2nd phase insulin secretion.
“Rather than rapidly declining to basal levels, insulin secretion elicited by the combination of high-[K+]o depolarization and glucose exhibited a sustained 2nd phase insulin secretion (268).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [268]
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Cites
Dynamics of Insulin Secretion by the Perfused Rat Pancreas
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“In mouse islets, glucose-induced rise in [Ca(2) ]i displays a biphasic time course: an initial sustained elevation is followed by oscillations or by a lower plateau, depending on the glucose concentration (8,24,30,31).”
BackgroundRavier, M. A., Gilon, P., & Henquin, J. C. (1999) · Diabetes · doi:10.2337/diabetes.48.12.2374 · Cited by 48 · cited 3× · see citing works
“Similar observations have been made with single or groups of islets when [Ca(2) ]i was intermittently raised in the presence of higher glucose concentrations (39,40).”
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Research works printed but not linked: 1
- Panten U, Lenzen S: Alterations in energy metabolism of secretory cells. In Energetics of Secretion Responses, Vol II. Akkerman J.-W. N., Ed. Boca Raton, Florida, CRC Press, 1988, p. 109 -123
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Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men
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Regulation of two insulin granule populations within the reserve pool by distinct calcium sources
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Synaptotagmin-7 Functions to Replenish Insulin Granules for Exocytosis in Human Islet β-Cells
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- Authors
- Henquin, J.-C., Ishiyama, N., Nenquin, M., Ravier, M. A., & Jonas, J.-C.
- Affiliations
- UCLouvain (BE)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2002-02-01
- Volume
- 51
- Issue
- suppl_1
- Pages
- S60-S67
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2123767112
- Cited by
- 196
- References
- 4
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 13 · 2023: 8 · 2022: 7 · 2021: 8 · 2020: 10 · 2019: 7 · 2018: 3 · 2017: 9 · 2016: 4 · 2015: 11 · 2014: 7 · 2013: 14 · 2012: 8
- FWCI
- 1.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- DIAL (Catholic University of Leuven) (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- biphasic insulin secretion, pancreatic beta cells, glucose stimulation, stimulus-secretion coupling, intracellular calcium, insulin secretion, species differences
- MeSH terms
- Insulin Secretion, Animals, Calcium, Glucose, Insulin, Islets of Langerhans, Signal Transduction
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