Evidence that glucose can control insulin release independently from its action on ATP-sensitive K+ channels in mouse B cells.
Open accessAbstract
Glucose stimulation of insulin release involves closure of ATP-sensitive K+ channels, depolarization, and Ca2+ influx in B cells. Mouse islets were used to investigate whether glucose can still regulate insulin release when it cannot control ATP-sensitive K+ channels. Opening of these channels by diazoxide (100-250 mumol/liter) blocked the effects of glucose on B cell membrane potential (intracellular microelectrodes), free cytosolic Ca2+ (fura-2 method), and insulin release, but it did not prevent those of high K (30 mmol/liter). K-induced insulin release in the presence of diazoxide was, however, dose dependently increased by glucose, which was already effective at concentrations (2-6 mmol/liter) that are subthreshold under normal conditions (low K and no diazoxide). This effect was not accompanied by detectable changes in B cell membrane potential. Measurements of 45Ca fluxes and cytosolic Ca2+ indicated that glucose slightly increased Ca2+ influx during the first minutes of depolarization by K, but not in the steady state when its effect on insulin release was the largest. In conclusion, there exists a mechanism by which glucose can control insulin release independently from changes in K(+)-ATP channel activity, in membrane potential, and in cytosolic Ca2+. This mechanism may serve to amplify the secretory response to the triggering signal (closure of K(+)-ATP channels--depolarization--Ca2+ influx) induced by glucose.
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Glucose has an amplifying effect on insulin secretion that does not require further elevation of [Ca2+]i.
“Glucose also has an amplifying effect, which does not require further elevation of [Ca 2ϩ ] i (22).”
From Paradoxical Stimulation of Glucagon Secretion by High Glucose Concentrations (2006) · cites this paper as [22]
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- Authors
- Gembal, M., Gilon, P., & Henquin, J. C.
- Affiliations
- UCLouvain (BE)
- Saarland University (DE)
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 1992-04-01
- Volume
- 89
- Issue
- 4
- Pages
- 1288-1295
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC442990
- OpenAlex
- W2124971376
- Cited by
- 494
- References
- 42
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 11 · 2023: 5 · 2022: 13 · 2021: 16 · 2020: 7 · 2019: 4 · 2018: 10 · 2017: 9 · 2016: 8 · 2015: 23 · 2014: 25 · 2013: 17 · 2012: 13
- FWCI
- 11.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion, other-oa)
- Funders
- Université Catholique de Louvain
- Fonds De La Recherche Scientifique - FNRS
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- glucose-stimulated insulin secretion, insulin secretion, ATP-sensitive potassium channels, diazoxide, pancreatic beta cells, membrane potential, intracellular calcium, calcium influx, pancreatic islets, signal amplification
- MeSH terms
- Insulin Secretion, Adenosine Triphosphate, Animals, Calcium, Cells, Cultured, Diazoxide, Glucose, Insulin, Islets of Langerhans, Membrane Potentials, Potassium Channels, Mice
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