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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, 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. ISSN 1550-4131
M Watkinson - Beta Cell Hubs Dictate Pancreatic Islet Responses to Glucose.pdf - Published Version
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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 |
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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: | https://eprints.keele.ac.uk/id/eprint/4774 |