Cited by 31Pancreatic function and diabetesCalcium signaling and nucleotide metabolismIon channel regulation and function

Effects of calcium buffering on glucose‐induced insulin release in mouse pancreatic islets: an approximation to the calcium sensor

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Pertusa, José A. G., Sanchez‐Andrés, Juan V., Martín, Franz, Soria, Bernat·1999·The Journal of Physiology

Abstract

1. The properties of the calcium sensor for glucose-induced insulin secretion have been studied using cell-permeant Ca2+ buffers with distinct kinetics and affinities. In addition, submembrane cytosolic Ca2+ distribution has been modelled after trains of glucose-induced action potential-like depolarizations. 2. Slow Ca2+ buffers (around 1 mmol l-1 intracellular concentration) with different affinities (EGTA and Calcium Orange-5N) did not significantly affect glucose-induced insulin release. Modelling showed no effect on cytosolic Ca2+ concentrations at the outermost shell (0.05 microm), their effects being observed in the innermost shells dependent on Ca2+ affinity. 3. In contrast, fast Ca2+ buffers (around 1 mmol l-1 intracellular concentration) with different affinities (BAPTA and Calcium Green-5N) caused a 50 % inhibition of early insulin response and completely blocked the late phase of glucose-induced insulin response, their simulations showing a decrease of [Ca2+]i at both the inner and outermost shells. 4. These data are consistent with the existence in pancreatic beta-cells of a higher affinity Ca2+ sensor than that proposed for neurons. Moreover, these data are consistent with the proposed existence of two distinct pools of granules: (i) 'primed' vesicles, colocalized with Ca2+ channels and responsible of the first phase of insulin release; and (ii) 'reserved pool' vesicles, not colocalized and responsible for the second phase.

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  • Regulation of rapid insulin granule exocytosis by [Ca2+]i close to the Ca2+ channel would be consistent with the observed low Ca2+ sensitivity of exocytosis and the finding that 1st phase (but not 2nd phase) insulin secretion is resistant to EGTA but is inhibited by BAPTA.

    “Regulation of rapid insulin granule exocytosis by [Ca2+]i close to the Ca2+ channel would be consistent with the observed low Ca2+ sensitivity of exocytosis (tens of micromolar) and the finding that 1st phase (but not 2nd phase) insulin secretion is resistant to introduction of the slow Ca2+ chelator EGTA but is inhibited by the fast chelator BAPTA (510) (illustrated schematically in Figure 20C).”

    From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [510]

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Cited by

Sorted by citations

Authors
Pertusa, J. A. G., Sanchez‐Andrés, J. V., Martín, F., & Soria, B.
Affiliations
Universitat de Miguel Hernández d'Elx (ES)
Corresponding author
Soria, Bernat
Venue
The Journal of Physiology
Publisher
Wiley
Published
1999-10
Volume
520
Issue
2
Pages
473-483
ISSN
  • 0022-3751 (ISSN-L)
  • 1469-7793
OpenAlex
W2046008078
Cited by
31
References
0
Citations by year
2025: 2 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 1 · 2017: 2 · 2015: 1 · 2012: 1
FWCI
2.10
Type
journal article
Language
en
Open access
Locations
  • The Journal of Physiology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (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 › Molecular Biology › Ion channel regulation and function
Keywords
calcium buffering, glucose-stimulated insulin secretion, pancreatic beta cells, calcium sensor, intracellular calcium distribution, EGTA, BAPTA
MeSH terms
Animals, Calcium, Cells, Cultured, Chelating Agents, Egtazic Acid, Fluorescent Dyes, Glucose, Insulin, Islets of Langerhans, Male, Membrane Potentials, Models, Theoretical, Organic Chemicals, Mice

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