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Beta Cell Hubs Dictate Pancreatic Islet Responses to Glucose

Watkinson

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Authors

Watkinson



Abstract

The arrangement of ß cells within islets of Langerhans is critical for insulin release through the generation of rhythmic activity. A privileged role for individual ß cells in orchestrating these responses has long been suspected, but not directly demonstrated. We show here that the ß 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 ß cell dysfunction. Thus, the islet is wired by hubs, whose failure may contribute to type 2 diabetes mellitus.

Acceptance Date Jun 23, 2016
Publication Date Jul 21, 2016
Journal Cell Metabolism
Print ISSN 1550-4131
Publisher Elsevier
Pages 389 - 401
DOI https://doi.org/10.1016/j.cmet.2016.06.020
Keywords islets, insulin, ß cells, diabetes, optogenetics, imaging
Publisher URL https://doi.org/10.1016/j.cmet.2016.06.020

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