PUBLICATION
Optogenetic β cell interrogation in vivo reveals a functional hierarchy directing the Ca2+ response to glucose supported by vitamin B6
- Authors
- Delgadillo-Silva, L.F., Tasöz, E., Singh, S.P., Chawla, P., Georgiadou, E., Gompf, A., Rutter, G.A., Ninov, N.
- ID
- ZDB-PUB-240627-9
- Date
- 2024
- Source
- Science advances 10: eado4513eado4513 (Journal)
- Registered Authors
- Ninov, Nikolay, Singh, Sumeet Pal
- Keywords
- none
- Datasets
- GEO:GSE237867
- MeSH Terms
-
- Animals
- Calcium*/metabolism
- Calcium Signaling
- Glucose*/metabolism
- Insulin-Secreting Cells*/metabolism
- Optogenetics*
- Zebrafish*
- PubMed
- 38924394 Full text @ Sci Adv
Citation
Delgadillo-Silva, L.F., Tasöz, E., Singh, S.P., Chawla, P., Georgiadou, E., Gompf, A., Rutter, G.A., Ninov, N. (2024) Optogenetic β cell interrogation in vivo reveals a functional hierarchy directing the Ca2+ response to glucose supported by vitamin B6. Science advances. 10:eado4513eado4513.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping