Priming of insulin granules for exocytosis by granular Cl(-) uptake and acidification.
ATP-dependent priming of the secretory granules precedes Ca(2+)-regulated neuroendocrine secretion, but the exact nature of this reaction is not fully established in all secretory cell types. We have further investigated this reaction in the insulin-secreting pancreatic B-cell and demonstrate that g...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2001
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| _version_ | 1826306432472973312 |
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| author | Barg, S Huang, P Eliasson, L Nelson, D Obermüller, S Rorsman, P Thévenod, F Renström, E |
| author_facet | Barg, S Huang, P Eliasson, L Nelson, D Obermüller, S Rorsman, P Thévenod, F Renström, E |
| author_sort | Barg, S |
| collection | OXFORD |
| description | ATP-dependent priming of the secretory granules precedes Ca(2+)-regulated neuroendocrine secretion, but the exact nature of this reaction is not fully established in all secretory cell types. We have further investigated this reaction in the insulin-secreting pancreatic B-cell and demonstrate that granular acidification driven by a V-type H(+)-ATPase in the granular membrane is a decisive step in priming. This requires simultaneous Cl(-) uptake through granular ClC-3 Cl(-) channels. Accordingly, granule acidification and priming are inhibited by agents that prevent transgranular Cl(-) fluxes, such as 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and an antibody against the ClC-3 channels, but accelerated by increases in the intracellular ATP:ADP ratio or addition of hypoglycemic sulfonylureas. We suggest that this might represent an important mechanism for metabolic regulation of Ca(2+)-dependent exocytosis that is also likely to be operational in other secretory cell types. |
| first_indexed | 2024-03-07T06:47:53Z |
| format | Journal article |
| id | oxford-uuid:fb795447-d446-42b9-8402-0887fdd9200f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:47:53Z |
| publishDate | 2001 |
| record_format | dspace |
| spelling | oxford-uuid:fb795447-d446-42b9-8402-0887fdd9200f2022-03-27T13:14:09ZPriming of insulin granules for exocytosis by granular Cl(-) uptake and acidification.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:fb795447-d446-42b9-8402-0887fdd9200fEnglishSymplectic Elements at Oxford2001Barg, SHuang, PEliasson, LNelson, DObermüller, SRorsman, PThévenod, FRenström, EATP-dependent priming of the secretory granules precedes Ca(2+)-regulated neuroendocrine secretion, but the exact nature of this reaction is not fully established in all secretory cell types. We have further investigated this reaction in the insulin-secreting pancreatic B-cell and demonstrate that granular acidification driven by a V-type H(+)-ATPase in the granular membrane is a decisive step in priming. This requires simultaneous Cl(-) uptake through granular ClC-3 Cl(-) channels. Accordingly, granule acidification and priming are inhibited by agents that prevent transgranular Cl(-) fluxes, such as 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and an antibody against the ClC-3 channels, but accelerated by increases in the intracellular ATP:ADP ratio or addition of hypoglycemic sulfonylureas. We suggest that this might represent an important mechanism for metabolic regulation of Ca(2+)-dependent exocytosis that is also likely to be operational in other secretory cell types. |
| spellingShingle | Barg, S Huang, P Eliasson, L Nelson, D Obermüller, S Rorsman, P Thévenod, F Renström, E Priming of insulin granules for exocytosis by granular Cl(-) uptake and acidification. |
| title | Priming of insulin granules for exocytosis by granular Cl(-) uptake and acidification. |
| title_full | Priming of insulin granules for exocytosis by granular Cl(-) uptake and acidification. |
| title_fullStr | Priming of insulin granules for exocytosis by granular Cl(-) uptake and acidification. |
| title_full_unstemmed | Priming of insulin granules for exocytosis by granular Cl(-) uptake and acidification. |
| title_short | Priming of insulin granules for exocytosis by granular Cl(-) uptake and acidification. |
| title_sort | priming of insulin granules for exocytosis by granular cl uptake and acidification |
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