UNIGE document Scientific Article
previous document  unige:100304  next document
add to browser collection

Beta Cell Hubs Dictate Pancreatic Islet Responses to Glucose

Johnston, Natalie R
Mitchell, Ryan K
Haythorne, Elizabeth
Pessoa, Maria Paiva
Semplici, Francesca
Ferrer, Jorge
Piemonti, Lorenzo
Marchetti, Piero
show hidden authors show all authors [1 - 17]
Published in Cell Metabolism. 2016, vol. 24, no. 3, p. 389-401
Abstract The arrangement of β cells within islets of Langerhans is critical for insulin release through the generation of rhythmic activity. A privileged role for individual β cells in orchestrating these responses has long been suspected, but not directly demonstrated. We show here that the β cell population in situ is operationally heterogeneous. Mapping of islet functional architecture revealed the presence of hub cells with pacemaker properties, which remain stable over recording periods of 2 to 3 hr. Using a dual optogenetic/photopharmacological strategy, silencing of hubs abolished coordinated islet responses to glucose, whereas specific stimulation restored communication patterns. Hubs were metabolically adapted and targeted by both pro-inflammatory and glucolipotoxic insults to induce widespread β cell dysfunction. Thus, the islet is wired by hubs, whose failure may contribute to type 2 diabetes mellitus.
Keywords AnimalsCalcium Signaling/drug effects/radiation effectsCell Differentiation/drug effectsComputer SystemsDiabetes Mellitus/pathologyGlucose/pharmacologyHomeostasis/drug effects/radiation effectsHumansInsulin/secretionInsulin-Secreting Cells/drug effects/metabolismLightLipids/toxicityMetabolome/drug effectsMetabolomicsMiceOptical PhenomenaPhenotypeSpecies Specificity
PMID: 27452146
Full text
Article (Published version) (3.7 MB) - public document Free access
Research groups Création de tissus par bio-ingénieurie et régénération d'organes (1021)
La transplantation d'îlots de Langerhans (623)
(ISO format)
JOHNSTON, Natalie R et al. Beta Cell Hubs Dictate Pancreatic Islet Responses to Glucose. In: Cell Metabolism, 2016, vol. 24, n° 3, p. 389-401. doi: 10.1016/j.cmet.2016.06.020 https://archive-ouverte.unige.ch/unige:100304

307 hits



Deposited on : 2017-12-14

Export document
Format :
Citation style :