Optogenetic β cell interrogation in vivo reveals a functional hierarchy directing the Ca2+ response to glucose supported by vitamin B6.
Sci. Adv. 10:eado4513 (2024)
Coordination of cellular activity through Ca2+ enables β cells to secrete precise quantities of insulin. To explore how the Ca2+ response is orchestrated in space and time, we implement optogenetic systems to probe the role of individual β cells in the glucose response. By targeted β cell activation/inactivation in zebrafish, we reveal a hierarchy of cells, each with a different level of influence over islet-wide Ca2+ dynamics. First-responder β cells lie at the top of the hierarchy, essential for initiating the first-phase Ca2+ response. Silencing first responders impairs the Ca2+ response to glucose. Conversely, selective activation of first responders demonstrates their increased capability to raise pan-islet Ca2+ levels compared to followers. By photolabeling and transcriptionally profiling β cells that differ in their thresholds to a glucose-stimulated Ca2+ response, we highlight vitamin B6 production as a signature pathway of first responders. We further define an evolutionarily conserved requirement for vitamin B6 in enabling the Ca2+ response to glucose in mammalian systems.
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Publication type
Article: Journal article
Document type
Scientific Article
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Editors
Keywords
Pancreatic-islets; Dynamics; Insulin; Transcription; Oscillations; Networks; Health; Leader; Waves
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Language
english
Publication Year
2024
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0
HGF-reported in Year
2024
ISSN (print) / ISBN
2375-2548
e-ISSN
2375-2548
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Volume: 10,
Issue: 26,
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Article Number: eado4513
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American Association for the Advancement of Science (AAAS)
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Washington, DC [u.a.]
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Peer reviewed
Institute(s)
Institute of Pancreatic Islet Research (IPI)
POF-Topic(s)
90000 - German Center for Diabetes Research
Research field(s)
Helmholtz Diabetes Center
PSP Element(s)
G-502600-010
Grants
Canadian Institutes of Health Research (CIHR) postdoctoral fellowship Award
DFG - International Research Training Group
Wellcome Trust Investigator Award
UK MRC Programme
Diabetes UK Project
CRCHUM start-up funds, an Innovation Canada John R. Evans Leader Award
NIH-NIDDK multi-PI project
CIHR-JDRF Team
DFG
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Erfassungsdatum
2024-06-27