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Delgadillo-Silva, L.F. ; Tasöz, E. ; Singh, S.P.* ; Chawla, P.* ; Georgiadou, E.* ; Gompf, A.* ; Rutter, G.A.* ; Ninov, N.

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)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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
Corresponding Author
Keywords Pancreatic-islets; Dynamics; Insulin; Transcription; Oscillations; Networks; Health; Leader; Waves
ISSN (print) / ISBN 2375-2548
e-ISSN 2375-2548
Journal Science Advances
Quellenangaben Volume: 10, Issue: 26, Pages: , Article Number: eado4513 Supplement: ,
Publisher American Association for the Advancement of Science (AAAS)
Publishing Place Washington, DC [u.a.]
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute for Pancreatic Beta Cell Research (IPI)
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