CAPS1 and CAPS2 regulate stability and recruitment of insulin granules in mouse pancreatic beta cells.
CAPS1 and CAPS2 regulate dense-core vesicle release of transmitters and hormones in neuroendocrine cells, but their precise roles in the secretory process remain enigmatic. Here we show that CAPS2(-/-) and CAPS1(+/-);CAPS2(-/-) mice, despite having increased insulin sensitivity, are glucose intolera...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2008
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| _version_ | 1797076299801427968 |
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| author | Speidel, D Salehi, A Obermueller, S Lundquist, I Brose, N Renström, E Rorsman, P |
| author_facet | Speidel, D Salehi, A Obermueller, S Lundquist, I Brose, N Renström, E Rorsman, P |
| author_sort | Speidel, D |
| collection | OXFORD |
| description | CAPS1 and CAPS2 regulate dense-core vesicle release of transmitters and hormones in neuroendocrine cells, but their precise roles in the secretory process remain enigmatic. Here we show that CAPS2(-/-) and CAPS1(+/-);CAPS2(-/-) mice, despite having increased insulin sensitivity, are glucose intolerant and that this effect is attributable to a marked reduction of glucose-induced insulin secretion. This correlates with diminished Ca(2+)-dependent exocytosis, a reduction in the size of the morphologically docked pool, a decrease in the readily releasable pool of secretory vesicles, slowed granule priming, and suppression of second-phase (but not first-phase) insulin secretion. In beta cells of CAPS1(+/-);CAPS2(-/-) mice, the lowered insulin content and granule numbers were associated with an increase in lysosome numbers and lysosomal enzyme activity. We conclude that although CAPS proteins are not required for Ca(2+)-dependent exocytosis to proceed, they exert a modulatory effect on insulin granule priming, exocytosis, and stability. |
| first_indexed | 2024-03-07T00:02:07Z |
| format | Journal article |
| id | oxford-uuid:764d0c44-ea93-4019-812f-7b28b617797f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:02:07Z |
| publishDate | 2008 |
| record_format | dspace |
| spelling | oxford-uuid:764d0c44-ea93-4019-812f-7b28b617797f2022-03-26T20:14:59ZCAPS1 and CAPS2 regulate stability and recruitment of insulin granules in mouse pancreatic beta cells.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:764d0c44-ea93-4019-812f-7b28b617797fEnglishSymplectic Elements at Oxford2008Speidel, DSalehi, AObermueller, SLundquist, IBrose, NRenström, ERorsman, PCAPS1 and CAPS2 regulate dense-core vesicle release of transmitters and hormones in neuroendocrine cells, but their precise roles in the secretory process remain enigmatic. Here we show that CAPS2(-/-) and CAPS1(+/-);CAPS2(-/-) mice, despite having increased insulin sensitivity, are glucose intolerant and that this effect is attributable to a marked reduction of glucose-induced insulin secretion. This correlates with diminished Ca(2+)-dependent exocytosis, a reduction in the size of the morphologically docked pool, a decrease in the readily releasable pool of secretory vesicles, slowed granule priming, and suppression of second-phase (but not first-phase) insulin secretion. In beta cells of CAPS1(+/-);CAPS2(-/-) mice, the lowered insulin content and granule numbers were associated with an increase in lysosome numbers and lysosomal enzyme activity. We conclude that although CAPS proteins are not required for Ca(2+)-dependent exocytosis to proceed, they exert a modulatory effect on insulin granule priming, exocytosis, and stability. |
| spellingShingle | Speidel, D Salehi, A Obermueller, S Lundquist, I Brose, N Renström, E Rorsman, P CAPS1 and CAPS2 regulate stability and recruitment of insulin granules in mouse pancreatic beta cells. |
| title | CAPS1 and CAPS2 regulate stability and recruitment of insulin granules in mouse pancreatic beta cells. |
| title_full | CAPS1 and CAPS2 regulate stability and recruitment of insulin granules in mouse pancreatic beta cells. |
| title_fullStr | CAPS1 and CAPS2 regulate stability and recruitment of insulin granules in mouse pancreatic beta cells. |
| title_full_unstemmed | CAPS1 and CAPS2 regulate stability and recruitment of insulin granules in mouse pancreatic beta cells. |
| title_short | CAPS1 and CAPS2 regulate stability and recruitment of insulin granules in mouse pancreatic beta cells. |
| title_sort | caps1 and caps2 regulate stability and recruitment of insulin granules in mouse pancreatic beta cells |
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