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Cited by 227Pancreatic function and diabetesCellular transport and secretionCalcium signaling and nucleotide metabolism

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A Subset of 50 Secretory Granules in Close Contact With l-Type Ca2+ Channels Accounts for First-Phase Insulin Secretion in Mouse β-Cells

Barg, Sebastian, Eliasson, Lena, Renström, Erik, Rorsman, Patrik·2002·Diabetes
DOI 10.2337/diabetes.51.2007.s74
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Abstract

Capacitance measurements were applied to mouse pancreatic beta-cells to elucidate the cellular mechanisms underlying biphasic insulin secretion. We report here that only 10,000 granules are immediately available for release. The releasable granules tightly associate with the voltage-gated alpha(1C) Ca(2+) channels, and it is proposed that the release of these granules accounts for first-phase insulin secretion. Subsequent replenishment of the releasable pool by priming of previously nonreleasable granules is required for second-phase insulin secretion. The latter reaction depends on intragranular acidification due to the concerted action of granular bafilomycin-sensitive v-type H(+)-ATPase and 4,4-diisothiocyanostilbene-2,2-disulfonate--blockable ClC-3 Cl(-) channels. Lowering the cytoplasmic ATP/ADP ratio prevents granule acidification, granule priming, and refilling of the releasable pool. The latter finding provides an explanation to the transient nature of insulin secretion elicited by, for example, high extracellular K(+) in the absence of metabolizable fuels.

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Metadata

Authors
Barg, S., Eliasson, L., Renström, E., & Rorsman, P.
Affiliations
  • Lund University (SE)
  • From the Department of Molecular and Cellular Physiology, Institute of Physiology, Lund University, Lund, Sweden
ORCID
Venue
Diabetes
Publisher
American Diabetes Association
Published
2002-02-01
Volume
51
Issue
suppl_1
Pages
S74-S82
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/diabetes.51.2007.s74
OpenAlex
W2050076638
Cited by
227
References
0
Citations by year
2026: 2 · 2025: 4 · 2024: 6 · 2023: 4 · 2022: 5 · 2021: 9 · 2020: 4 · 2019: 10 · 2018: 5 · 2017: 7 · 2016: 7 · 2015: 14 · 2014: 6 · 2013: 8 · 2012: 14
FWCI
3.18
Type
journal article
Language
en
Open access
closed
Locations
  • Diabetes (publishedVersion)
  • PubMed (publishedVersion)
  • Lund University Publications (Lund University) (submittedVersion)
Funders
Vetenskapsrådet
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › 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, secretory granules, L-type calcium channels, first-phase insulin secretion, second-phase insulin secretion, pancreatic beta cells, V-ATPase, ClC-3 chloride channel, ATP/ADP ratio
MeSH terms
Insulin Secretion, Animals, Insulin, Islets of Langerhans, Calcium Channels, L-Type, Secretory Vesicles, Mice

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