Cited by 90Pancreatic function and diabetesCellular transport and secretionCalcium signaling and nucleotide metabolism

Effects of Intravesicular H+ and Extracellular H+ and Zn2+ on Insulin Secretion in Pancreatic Beta Cells

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Aspinwall, Craig A., Brooks, Sunday A., Kennedy, Robert T., Lakey, Jonathan R.T.·1997·Journal of Biological Chemistry

Abstract

The effects of extracellular Zn2+ and pH and intravesicular pH on insulin and 5-hydroxytryptamine (5-HT) secretion from pancreatic beta cells were investigated. Insulin and 5-HT secretion from single cells was detected by amperometry as a series of current spikes corresponding to detection of multimolecular packets secreted by exocytosis. Spike width was used as a measure of the kinetics of clearance from the cell and the area of spikes as a measure of amount released. Changes in extracellular pH from 6.9 to 7.9 caused insulin spikes to become narrower with no change in area, whereas the same treatments had no effect on 5-HT secretion. Treatment of cells with Bafilomycin A1 or N-ethylmaleimide, both of which are expected to increase intravesicular pH by inhibiting V-type H+-ATPase, had no effect on 5-HT secretion but caused insulin spikes to become more narrow. These results indicate that exposure to high pH, whether intravesicular or extracellular, accelerates release of insulin during exocytosis without affecting the amount of insulin released. Increasing extracellular Zn2+ concentration from 0 to 25 microM increased the width and decreased the area of insulin spikes without affecting 5-HT secretion. Zn2+ effects were likely exerted through a common-ion effect on Zn2+-insulin dissociation. It was concluded that intravesicular storage conditions and extracellular ions can affect free insulin concentration in the vicinity of beta cells during secretion.

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  • Carbon fiber amperometry has been successfully applied to rodent β-cells in which the granules have been preloaded with serotonin.

    “This technique has been successfully applied to rodent β-cells in which the granules have preloaded with serotonin (36, 74, 634, 663) and modified carbon fibers have been used to detect the release of insulin itself (294).”

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Research works printed but not linked: 6

  1. Wightman, R. M., Jankowski, J. A., Kennedy, R. T., Kawagoe, K. T., Schroeder, T. J., Leszczyszyn, D. J., Near, J. A., Diliberto, E. J., and Viveros, O. H. (1991) Proc. Natl. Acad. Sci. U. S. A. 88, 10754 -10758
  2. Zhou, Z., and Misler, S. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 6938 -6942
  3. Huang, L., Shen, H., Atkinson, M. A., and Kennedy, R. T. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 608 -612
  4. Warnock, G. L., Ao, Z., Lakey, J. R. T., and Rajotte, R. V. (1994) in Pancreatic Islet Transplantation Vol I: Procurement of Pancreatic Islets (Lanza, R. P., and Chick, W. L., eds) pp. 81-95, R. G. Landes, Austin, TX 42.
  5. Bowman, E. J., Siebers, A., and Altendorf, K. (1988) Proc. Natl. Acad. Sci.
  6. Hazelwood, R. L. (1989) The Endocrine Pancreas Prentice Hall, Englewood Cliffs, NJ

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Authors
Aspinwall, C. A., Brooks, S. A., Kennedy, R. T., & Lakey, J. R. T.
Affiliations
  • University of Florida (US)
  • University of Alberta (CA)
Corresponding author
Kennedy, Robert T.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1997-12
Volume
272
Issue
50
Pages
31308-31314
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2045267378
Cited by
90
References
1
Citations by year
2025: 2 · 2024: 1 · 2022: 3 · 2021: 4 · 2020: 3 · 2019: 1 · 2017: 2 · 2016: 4 · 2015: 4 · 2014: 2 · 2013: 3 · 2012: 1
FWCI
7.66
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Fondation pour la Recherche Médicale
  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK046960, R0 1DK46960-01)
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 › Physiology › Calcium signaling and nucleotide metabolism
Keywords
insulin secretion, pancreatic beta cells, intravesicular pH, extracellular pH, zinc, exocytosis, V-type H+-ATPase, bafilomycin A1, N-ethylmaleimide, common ion effect, amperometry
MeSH terms
Insulin Secretion, Animals, Anti-Bacterial Agents, Cells, Cultured, Dogs, Enzyme Inhibitors, Ethylmaleimide, Exocytosis, Proton-Translocating ATPases, Hydrogen, Hydrogen-Ion Concentration, Insulin, Islets of Langerhans, Serotonin, Zinc, Macrolides

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