Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/115075
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dc.contributor.authorAcreman, Samuel-
dc.contributor.authorMa, Jinfang-
dc.contributor.authorDenwood, Geoffrey-
dc.contributor.authorGao, Rui-
dc.contributor.authorTarasov, Andrei-
dc.contributor.authorRorsman, Patrik-
dc.contributor.authorZhang, Quan-
dc.date.accessioned2024-04-30T10:25:24Z-
dc.date.available2024-04-30T10:25:24Z-
dc.date.issued2024-05-17-
dc.identifier.issn25890042pt
dc.identifier.urihttps://hdl.handle.net/10316/115075-
dc.description.abstractGlucagon 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.isoengpt
dc.publisherElsevierpt
dc.relationThis 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.rightsopenAccesspt
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt
dc.subjectCell biology; Cellular physiology; Physiologypt
dc.titleThe endoplasmic reticulum plays a key role in α-cell intracellular Ca2+ dynamics and glucose-regulated glucagon secretion in mouse isletspt
dc.typearticle-
degois.publication.firstPage109665pt
degois.publication.issue5pt
degois.publication.titleiSciencept
dc.peerreviewedyespt
dc.identifier.doi10.1016/j.isci.2024.109665pt
degois.publication.volume27pt
dc.date.embargo2024-05-17*
uc.date.periodoEmbargo0pt
item.fulltextCom Texto completo-
item.grantfulltextopen-
item.languageiso639-1en-
item.openairetypearticle-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.orcid0000-0002-3626-4855-
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais
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