Optogenetic ß cell interrogation in vivo reveals a functional hierarchy directing the Ca2+ response to glucose supported by vitamin B6.
Sci Adv
; 10(26): eado4513, 2024 Jun 28.
Article
in En
| MEDLINE
| ID: mdl-38924394
ABSTRACT
Coordination of cellular activity through Ca2+ enables ß 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 ß cells in the glucose response. By targeted ß 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 ß 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 ß 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Zebrafish
/
Calcium
/
Insulin-Secreting Cells
/
Optogenetics
/
Glucose
Limits:
Animals
Language:
En
Journal:
Sci Adv
Year:
2024
Document type:
Article
Affiliation country:
Alemania