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

Author:
  • Xingjun Jing
  • Dai-Qing Li
  • Charlotta Olofsson
  • Albert Salehi
  • Vikas Surve
  • José Caballero
  • Rosita Ivarsson
  • Ingmar Lundquist
  • Alexey Pereverzev
  • Toni Schneider
  • Patrik Rorsman
  • Erik Renström
Publishing year: 2005
Language: English
Pages: 146-154
Publication/Series: Journal of Clinical Investigation
Volume: 115
Issue: 1
Document type: Journal article
Publisher: The Journal of Clinical Investigation

Abstract english

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.

Keywords

  • Endocrinology and Diabetes

Other

Published
  • Islet patophysiology
  • Vascular Physiology
  • ISSN: 0021-9738
Erik Renström
E-mail: erik [dot] renstrom [at] med [dot] lu [dot] se

Deputy head of department

Department of Clinical Sciences, Malmö

+46 40 39 11 57

+46 40 39 11 57

Principal investigator

Islet patophysiology

+46 40 39 11 57

+46 40 39 11 57

20-3-308

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Lund University Diabetes Centre, CRC, SUS Malmö, Entrance 72, House 91:12. SE-205 02 Malmö. Telephone: +46 40 39 10 00