PuSH - Publication Server of Helmholtz Zentrum München

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.
Impact Factor
Scopus SNIP
Altmetric
11.700
0.000
Tags
Annotations
Special Publikation
Hide on homepage

Edit extra information
Edit own tags
Private
Edit own annotation
Private
Hide on publication lists
on hompage
Mark as special
publikation
Publication type Article: Journal article
Document type Scientific Article
Keywords Pancreatic-islets; Dynamics; Insulin; Transcription; Oscillations; Networks; Health; Leader; Waves
Language english
Publication Year 2024
HGF-reported in Year 2024
ISSN (print) / ISBN 2375-2548
e-ISSN 2375-2548
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.]
Reviewing status 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
Scopus ID 85197107121
PubMed ID 38924394
Erfassungsdatum 2024-06-27