CaV2.3 calcium channels control second-phase insulin release.
Concerted activation of different voltage-gated Ca( (2+) ) channel isoforms may determine the kinetics of insulin release from pancreatic islets. Here we have elucidated the role of R-type Ca(V)2.3 channels in that process. A 20% reduction in glucose-evoked insulin secretion was observed in Ca(V)2.3...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2005
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| _version_ | 1826286610737528832 |
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| author | Jing, X Li, D Olofsson, C Salehi, A Surve, V Caballero, J Ivarsson, R Lundquist, I Pereverzev, A Schneider, T Rorsman, P Renström, E |
| author_facet | Jing, X Li, D Olofsson, C Salehi, A Surve, V Caballero, J Ivarsson, R Lundquist, I Pereverzev, A Schneider, T Rorsman, P Renström, E |
| author_sort | Jing, X |
| collection | OXFORD |
| description | Concerted activation of different voltage-gated Ca( (2+) ) channel isoforms may determine the kinetics of insulin release from pancreatic islets. Here we have elucidated the role of R-type Ca(V)2.3 channels in that process. A 20% reduction in glucose-evoked insulin secretion was observed in Ca(V)2.3-knockout (Ca(V)2.3(-/-)) islets, close to the 17% inhibition by the R-type blocker SNX482 but much less than the 77% inhibition produced by the L-type Ca(2+) channel antagonist isradipine. Dynamic insulin-release measurements revealed that genetic or pharmacological Ca(V)2.3 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 Ca(2+) signaling and a 25% reduction in granule recruitment after completion of the initial exocytotic burst in single Ca(V)2.3(-/-) beta cells. Ca(V)2.3 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 Ca(V)2.3(-/-) mouse. We propose a specific role for Ca(V)2.3 Ca(2+) channels in second-phase insulin release, that of mediating the Ca(2+) entry needed for replenishment of the releasable pool of granules as well as islet cell differentiation. |
| first_indexed | 2024-03-07T01:46:18Z |
| format | Journal article |
| id | oxford-uuid:988a8d5e-4763-4193-b13c-80d0e169c7cb |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:46:18Z |
| publishDate | 2005 |
| record_format | dspace |
| spelling | oxford-uuid:988a8d5e-4763-4193-b13c-80d0e169c7cb2022-03-27T00:07:44ZCaV2.3 calcium channels control second-phase insulin release.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:988a8d5e-4763-4193-b13c-80d0e169c7cbEnglishSymplectic Elements at Oxford2005Jing, XLi, DOlofsson, CSalehi, ASurve, VCaballero, JIvarsson, RLundquist, IPereverzev, ASchneider, TRorsman, PRenström, EConcerted activation of different voltage-gated Ca( (2+) ) channel isoforms may determine the kinetics of insulin release from pancreatic islets. Here we have elucidated the role of R-type Ca(V)2.3 channels in that process. A 20% reduction in glucose-evoked insulin secretion was observed in Ca(V)2.3-knockout (Ca(V)2.3(-/-)) islets, close to the 17% inhibition by the R-type blocker SNX482 but much less than the 77% inhibition produced by the L-type Ca(2+) channel antagonist isradipine. Dynamic insulin-release measurements revealed that genetic or pharmacological Ca(V)2.3 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 Ca(2+) signaling and a 25% reduction in granule recruitment after completion of the initial exocytotic burst in single Ca(V)2.3(-/-) beta cells. Ca(V)2.3 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 Ca(V)2.3(-/-) mouse. We propose a specific role for Ca(V)2.3 Ca(2+) channels in second-phase insulin release, that of mediating the Ca(2+) entry needed for replenishment of the releasable pool of granules as well as islet cell differentiation. |
| spellingShingle | Jing, X Li, D Olofsson, C Salehi, A Surve, V Caballero, J Ivarsson, R Lundquist, I Pereverzev, A Schneider, T Rorsman, P Renström, E CaV2.3 calcium channels control second-phase insulin release. |
| title | CaV2.3 calcium channels control second-phase insulin release. |
| title_full | CaV2.3 calcium channels control second-phase insulin release. |
| title_fullStr | CaV2.3 calcium channels control second-phase insulin release. |
| title_full_unstemmed | CaV2.3 calcium channels control second-phase insulin release. |
| title_short | CaV2.3 calcium channels control second-phase insulin release. |
| title_sort | cav2 3 calcium channels control second phase insulin release |
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