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A Subset of 50 Secretory Granules in Close Contact With L-Type Ca(2+) Channels Accounts for First-Phase Insulin Secretion in Mouse beta-Cells.

Barg, Sebastian LU ; Eliasson, Lena LU orcid ; Renström, Erik LU and Rorsman, Patrik LU (2002) In Diabetes 51 Suppl 1. p.74-82
Abstract
Capacitance measurements were applied to mouse pancreatic beta-cells to elucidate the cellular mechanisms underlying biphasic insulin secretion. We report here that only <50 of the beta-cell's >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... (More)
Capacitance measurements were applied to mouse pancreatic beta-cells to elucidate the cellular mechanisms underlying biphasic insulin secretion. We report here that only <50 of the beta-cell's >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. (Less)
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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes
volume
51 Suppl 1
pages
74 - 82
publisher
American Diabetes Association Inc.
external identifiers
  • wos:000173599900014
  • scopus:0036310678
ISSN
1939-327X
DOI
10.2337/diabetes.51.2007.S74
language
English
LU publication?
yes
id
786ae2b2-18a0-4691-9a42-a28f1c61df70 (old id 106380)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11815462&dopt=Abstract
date added to LUP
2016-04-01 15:51:17
date last changed
2022-02-05 03:26:48
@article{786ae2b2-18a0-4691-9a42-a28f1c61df70,
  abstract     = {{Capacitance measurements were applied to mouse pancreatic beta-cells to elucidate the cellular mechanisms underlying biphasic insulin secretion. We report here that only &lt;50 of the beta-cell's &gt;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.}},
  author       = {{Barg, Sebastian and Eliasson, Lena and Renström, Erik and Rorsman, Patrik}},
  issn         = {{1939-327X}},
  language     = {{eng}},
  pages        = {{74--82}},
  publisher    = {{American Diabetes Association Inc.}},
  series       = {{Diabetes}},
  title        = {{A Subset of 50 Secretory Granules in Close Contact With L-Type Ca(2+) Channels Accounts for First-Phase Insulin Secretion in Mouse beta-Cells.}},
  url          = {{http://dx.doi.org/10.2337/diabetes.51.2007.S74}},
  doi          = {{10.2337/diabetes.51.2007.S74}},
  volume       = {{51 Suppl 1}},
  year         = {{2002}},
}