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Title

Beta Cell Hubs Dictate Pancreatic Islet Responses to Glucose

Authors
Johnston, Natalie R
Mitchell, Ryan K
Haythorne, Elizabeth
Pessoa, Maria Paiva
Semplici, Francesca
Ferrer, Jorge
Piemonti, Lorenzo
Marchetti, Piero
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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
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PMID: 27452146
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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. https://archive-ouverte.unige.ch/unige:100304

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Deposited on : 2017-12-14

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