Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/115075
DC Field | Value | Language |
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dc.contributor.author | Acreman, Samuel | - |
dc.contributor.author | Ma, Jinfang | - |
dc.contributor.author | Denwood, Geoffrey | - |
dc.contributor.author | Gao, Rui | - |
dc.contributor.author | Tarasov, Andrei | - |
dc.contributor.author | Rorsman, Patrik | - |
dc.contributor.author | Zhang, Quan | - |
dc.date.accessioned | 2024-04-30T10:25:24Z | - |
dc.date.available | 2024-04-30T10:25:24Z | - |
dc.date.issued | 2024-05-17 | - |
dc.identifier.issn | 25890042 | pt |
dc.identifier.uri | https://hdl.handle.net/10316/115075 | - |
dc.description.abstract | Glucagon is secreted by pancreatic α-cells to counteract hypoglycaemia. How glucose regulates glucagon secretion remains unclear. Here, using mouse islets, we studied the role of transmembrane and endoplasmic reticulum (ER) Ca2+ on intrinsic α-cell glucagon secretion. Blocking isradipine-sensitive L-type voltage-gated Ca2+ (Cav) channels abolished α-cell electrical activity but had little impact on its cytosolic Ca2+ oscillations or low-glucose-stimulated glucagon secretion. In contrast, depleting ER Ca2+ with cyclopiazonic acid or blocking ER Ca2+-releasing ryanodine receptors abolished α-cell glucose sensitivity and low-glucose-stimulated glucagon secretion. ER Ca2+ mobilization in α-cells is regulated by intracellular ATP and likely to be coupled to Ca2+ influx through P/Q-type Cav channels. ω-Agatoxin IVA blocked α-cell ER Ca2+ release and cell exocytosis, but had no additive effect on glucagon secretion when combined with ryanodine. We conclude that glucose regulates glucagon secretion through the control of ER Ca2+ mobilization, a mechanism that can be independent of α-cell electrical activity. | pt |
dc.language.iso | eng | pt |
dc.publisher | Elsevier | pt |
dc.relation | This study was supported by a Diabetes UK RD Lawrence Fellowship (QZ, 14/0005128), an EFSD European Research Program on New Targets for Type 2 Diabetes supported by an educational research grant from MSD (Q.Z., 96406), a John Fell Fund project grant (Q.Z., 152/052), the RCUK Medical Research Council (PR, MR/VO11979/1), the Leona M. and Harry B. Helmsley Charitable Trust (PR, G-1912-03553& G-2305-06047), and a project grant from the National Natural Science Foundation of China (82200887) to R.G.. J.M. is supported by a visiting fellowship from Chinese Scholarship Council (CSC; 202106240129). | pt |
dc.rights | openAccess | pt |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | pt |
dc.subject | Cell biology; Cellular physiology; Physiology | pt |
dc.title | The endoplasmic reticulum plays a key role in α-cell intracellular Ca2+ dynamics and glucose-regulated glucagon secretion in mouse islets | pt |
dc.type | article | - |
degois.publication.firstPage | 109665 | pt |
degois.publication.issue | 5 | pt |
degois.publication.title | iScience | pt |
dc.peerreviewed | yes | pt |
dc.identifier.doi | 10.1016/j.isci.2024.109665 | pt |
degois.publication.volume | 27 | pt |
dc.date.embargo | 2024-05-17 | * |
uc.date.periodoEmbargo | 0 | pt |
item.fulltext | Com Texto completo | - |
item.grantfulltext | open | - |
item.languageiso639-1 | en | - |
item.cerifentitytype | Publications | - |
item.openairetype | article | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.orcid | 0000-0002-3626-4855 | - |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais |
Files in This Item:
File | Description | Size | Format | |
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The endoplasmic reticulum plays a key role in α-cell intracellular Ca2+ dynamics and glucose-regulated glucagon secretion in mouse islets.pdf | 2.33 MB | Adobe PDF | View/Open |
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