Johnston, N, Mitchell, R, Haythorne, E, Pessoa, M, Semplici, F, Ferrer, J, Piemonti, L, Marchetti, P, Buglani, M, Bosco, D, Berishvili, E, Duncanson, P, Watkinson, M ORCID: https://orcid.org/0000-0003-1877-5667, Broichhagen, J, Trauner, D, Rutter, G and Hodson, D (2016) Beta Cell Hubs Dictate Pancreatic Islet Responses to Glucose. Cell Metabolism, 24 (3). 389 - 401.

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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.

Item Type: Article
Additional Information: Open Access funded by Medical Research Council Under a Creative Commons license
Uncontrolled Keywords: islets, insulin, β cells, diabetes, optogenetics, imaging
Subjects: Q Science > QD Chemistry
R Medicine > RC Internal medicine > RC660 Diabetes
Divisions: Faculty of Natural Sciences > School of Chemical and Physical Sciences
Depositing User: Symplectic
Date Deposited: 19 Apr 2018 08:35
Last Modified: 10 Apr 2019 08:54
URI: http://eprints.keele.ac.uk/id/eprint/4774

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