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CaV2.3 calcium channels control second-phase insulin release.

Jing, Xingjun LU ; Li, Dai-Qing LU ; Olofsson, Charlotta LU ; Salehi, Albert; Surve, Vikas LU ; Caballero, José LU ; Ivarsson, Rosita LU ; Lundquist, Ingmar LU ; Pereverzev, Alexey and Schneider, Toni, et al. (2005) In Journal of Clinical Investigation 115(1). p.146-154
Abstract
Concerted activation of different voltage-gated Ca2+ channel isoforms may determine the kinetics of insulin release from pancreatic islets. Here we have elucidated the role of R-type CaV2.3 channels in that process. A 20% reduction in glucose-evoked insulin secretion was observed in CaV2.3-knockout (CaV2.3–/–) islets, close to the 17% inhibition by the R-type blocker SNX482 but much less than the 77% inhibition produced by the L-type Ca2+ channel antagonist isradipine. Dynamic insulin-release measurements revealed that genetic or pharmacological CaV2.3 ablation strongly suppressed second-phase secretion, whereas first-phase secretion was unaffected, a result also observed in vivo. Suppression of the second phase coincided with an 18%... (More)
Concerted activation of different voltage-gated Ca2+ channel isoforms may determine the kinetics of insulin release from pancreatic islets. Here we have elucidated the role of R-type CaV2.3 channels in that process. A 20% reduction in glucose-evoked insulin secretion was observed in CaV2.3-knockout (CaV2.3–/–) islets, close to the 17% inhibition by the R-type blocker SNX482 but much less than the 77% inhibition produced by the L-type Ca2+ channel antagonist isradipine. Dynamic insulin-release measurements revealed that genetic or pharmacological CaV2.3 ablation strongly suppressed second-phase secretion, whereas first-phase secretion was unaffected, a result also observed in vivo. Suppression of the second phase coincided with an 18% reduction in oscillatory Ca2+ signaling and a 25% reduction in granule recruitment after completion of the initial exocytotic burst in single CaV2.3–/– ß cells. CaV2.3 ablation also impaired glucose-mediated suppression of glucagon secretion in isolated islets (27% versus 58% in WT), an effect associated with coexpression of insulin and glucagon in a fraction of the islet cells in the CaV2.3–/– mouse. We propose a specific role for CaV2.3 Ca2+ channels in second-phase insulin release, that of mediating the Ca2+ entry needed for replenishment of the releasable pool of granules as well as islet cell differentiation. (Less)
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Journal of Clinical Investigation
volume
115
issue
1
pages
146 - 154
publisher
The Journal of Clinical Investigation
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  • pmid:15630454
  • wos:000226509000023
  • scopus:13744260502
ISSN
0021-9738
DOI
10.1172/JCI200522518
language
English
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yes
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1d30e4ef-86ee-4486-bc9f-2ae5ef777b79 (old id 133324)
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http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15630454&query_hl=2&itool=pubmed_docsum
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2007-07-13 15:53:26
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@article{1d30e4ef-86ee-4486-bc9f-2ae5ef777b79,
  abstract     = {Concerted activation of different voltage-gated Ca2+ channel isoforms may determine the kinetics of insulin release from pancreatic islets. Here we have elucidated the role of R-type CaV2.3 channels in that process. A 20% reduction in glucose-evoked insulin secretion was observed in CaV2.3-knockout (CaV2.3–/–) islets, close to the 17% inhibition by the R-type blocker SNX482 but much less than the 77% inhibition produced by the L-type Ca2+ channel antagonist isradipine. Dynamic insulin-release measurements revealed that genetic or pharmacological CaV2.3 ablation strongly suppressed second-phase secretion, whereas first-phase secretion was unaffected, a result also observed in vivo. Suppression of the second phase coincided with an 18% reduction in oscillatory Ca2+ signaling and a 25% reduction in granule recruitment after completion of the initial exocytotic burst in single CaV2.3–/– ß cells. CaV2.3 ablation also impaired glucose-mediated suppression of glucagon secretion in isolated islets (27% versus 58% in WT), an effect associated with coexpression of insulin and glucagon in a fraction of the islet cells in the CaV2.3–/– mouse. We propose a specific role for CaV2.3 Ca2+ channels in second-phase insulin release, that of mediating the Ca2+ entry needed for replenishment of the releasable pool of granules as well as islet cell differentiation.},
  author       = {Jing, Xingjun and Li, Dai-Qing and Olofsson, Charlotta and Salehi, Albert and Surve, Vikas and Caballero, José and Ivarsson, Rosita and Lundquist, Ingmar and Pereverzev, Alexey and Schneider, Toni and Rorsman, Patrik and Renström, Erik},
  issn         = {0021-9738},
  language     = {eng},
  number       = {1},
  pages        = {146--154},
  publisher    = {The Journal of Clinical Investigation},
  series       = {Journal of Clinical Investigation},
  title        = {CaV2.3 calcium channels control second-phase insulin release.},
  url          = {http://dx.doi.org/10.1172/JCI200522518},
  volume       = {115},
  year         = {2005},
}