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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.

Original publication

DOI

10.1016/j.cmet.2016.06.020

Type

Journal article

Journal

Cell Metab

Publication Date

13/09/2016

Volume

24

Pages

389 - 401

Keywords

diabetes, imaging, insulin, islets, optogenetics, β cells, Animals, Calcium Signaling, Cell Differentiation, Computer Systems, Diabetes Mellitus, Glucose, Homeostasis, Humans, Insulin, Insulin Secretion, Insulin-Secreting Cells, Light, Lipids, Metabolome, Metabolomics, Mice, Optical Phenomena, Phenotype, Species Specificity