| First Author | Delgadillo-Silva LF | Year | 2024 |
| Journal | Sci Adv | Volume | 10 |
| Issue | 26 | Pages | eado4513 |
| PubMed ID | 38924394 | Mgi Jnum | J:360395 |
| Mgi Id | MGI:7661954 | Doi | 10.1126/sciadv.ado4513 |
| Citation | Delgadillo-Silva LF, et al. (2024) Optogenetic beta cell interrogation in vivo reveals a functional hierarchy directing the Ca(2+) response to glucose supported by vitamin B6. Sci Adv 10(26):eado4513 |
| abstractText | Coordination of cellular activity through Ca(2+) enables beta cells to secrete precise quantities of insulin. To explore how the Ca(2+) response is orchestrated in space and time, we implement optogenetic systems to probe the role of individual beta cells in the glucose response. By targeted beta cell activation/inactivation in zebrafish, we reveal a hierarchy of cells, each with a different level of influence over islet-wide Ca(2+) dynamics. First-responder beta cells lie at the top of the hierarchy, essential for initiating the first-phase Ca(2+) response. Silencing first responders impairs the Ca(2+) response to glucose. Conversely, selective activation of first responders demonstrates their increased capability to raise pan-islet Ca(2+) levels compared to followers. By photolabeling and transcriptionally profiling beta cells that differ in their thresholds to a glucose-stimulated Ca(2+) 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 Ca(2+) response to glucose in mammalian systems. |
