ArticlePLoS biology2022
Functional architecture of pancreatic islets identifies a population of first responder cells that drive the first-phase calcium response.
Article in PLoS biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 58 citations in OpenAlex.
- Dysregulated glucagon signaling contributes to hypoglycemia after vertical sleeve gastrectomy in mice.Molecular metabolism · 2026Article
- Pancreatic α cells are required for nutrient homeostasis by regulating dynamic β cell networks in islets.Science advances · 2026Article
- Dielectrophoresis reveals stimulus-induced remodeling of insulin granule subpopulations.Biophysical journal · 2026Article
- Diminished gap junction coupling under diabetogenic conditions does not drive loss of functional β-cell subpopulations.The Journal of general physiology · 2026Article
- Pancreatic islet cell calcium ion imaging at single-cell resolution: functional identification of first-responder, highly connected ("hub"), and leader beta-cells.Frontiers in endocrinology · 2026Review
- ER calcium stores contribute to glucose-induced CaCell calcium · 2026Article
- Dielectrophoresis Reveals Stimulus-Induced Remodeling of Insulin Granule Subpopulations.bioRxiv : the preprint server for biology · 2025Article
- Identification of type 2 diabetes- and obesity-associated human β-cells using deep transfer learning.eLife · 2025Article
- Spatially bound functional heterogeneity drives modular organization in β-cell networks.Biophysical journal · 2025Article
- Efficient transduction of pancreas tissue slices with genetically encoded calcium integrators.bioRxiv : the preprint server for biology · 2025Article
- Localized GLP1 receptor pre-internalization directs pancreatic alpha cell to beta cell communication.Cell metabolism · 2025Article
- Glucokinase activity controls peripherally located subpopulations of β-cells that lead islet CaeLife · 2025Article
- Biphasic glucose-stimulated insulin secretion over decades: a journey from measurements and modeling to mechanistic insights.Life metabolism · 2025Review
- Glucokinase activity controls peripherally-located subpopulations of β-cells that lead islet CabioRxiv : the preprint server for biology · 2024Article
- Exploring pancreatic beta-cell subgroups and their connectivity.Nature metabolism · 2024Review
- Optogenetic β cell interrogation in vivo reveals a functional hierarchy directing the CaScience advances · 2024Article
- Extracellular matrix stiffness mediates insulin secretion in pancreatic islets via mechanosensitive Piezo1 channel regulated CaMatrix biology plus · 2024Article
- Differential CpG methylation at Nnat in the early establishment of beta cell heterogeneity.Diabetologia · 2024Article
- Network representation of multicellular activity in pancreatic islets: Technical considerations for functional connectivity analysis.PLoS computational biology · 2024Article
- The Importance of Intra-Islet Communication in the Function and Plasticity of the Islets of Langerhans during Health and Diabetes.International journal of molecular sciences · 2024Review
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Insulin-secreting β-cells are functionally heterogeneous. Whether there exist cells driving the first-phase calcium response in individual islets, has not been examined. We examine "first responder" cells, defined by the earliest [Ca2+] response during first-phase [Ca2+] elevation, distinct from previously identified "hub" and "leader" cells. We used islets isolated from Mip-CreER; Rosa-Stop-Lox-Stop-GCamP6s mice (β-GCamP6s) that show β-cell-specific GCamP6s expression following tamoxifen-induced CreER-mediated recombination. First responder cells showed characteristics of high membrane excitability and lower electrical coupling to their neighbors. The first-phase response time of β-cells in the islet was spatially organized, dependent on the cell's distance to the first responder cell, and consistent over time up to approximately 24 h. When first responder cells were laser ablated, the first-phase [Ca2+] was slowed down, diminished, and discoordinated compared to random cell ablation. Cells that were next earliest to respond often took over the role of the first responder upon ablation. In summary, we discover and characterize a distinct first responder β-cell state, critical for the islet first-phase response to glucose.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.