Cited by 494Pancreatic function and diabetesIon channel regulation and functionMetabolism, Diabetes, and Cancer

Evidence that glucose can control insulin release independently from its action on ATP-sensitive K+ channels in mouse B cells.

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Gembal, M, Gilon, P, Henquin, J C·1992·Journal of Clinical Investigation

Abstract

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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Authors
Gembal, M., Gilon, P., & Henquin, J. C.
Affiliations
  • UCLouvain (BE)
  • Saarland University (DE)
Venue
Journal of Clinical Investigation
Published
1992-04-01
Volume
89
Issue
4
Pages
1288-1295
ISSN
0021-9738 (ISSN-L)
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
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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