@article{Johnston:2016:10.1016/j.cmet.2016.06.020,
author = {Johnston, NR and Mitchell, RK and Haythorne, E and Pessoa, MP and Semplici, F and Ferrer, J and Piemonti, L and Marchetti, P and Bosco, D and Bugliani, M and Berishvilli, E and Duncanson, P and Watkinson, M and Broichhagen, J and Trauner, D and Rutter, GA and Hodson, DA},
doi = {10.1016/j.cmet.2016.06.020},
journal = {Cell Metabolism},
pages = {389--401},
title = {Beta cell hubs dictate pancreatic islet responses to glucose},
url = {http://dx.doi.org/10.1016/j.cmet.2016.06.020},
volume = {24},
year = {2016}
}

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TY  - JOUR
AB  - The arrangement of beta cells within islets of Langerhans is critical for insulin release through thegeneration of rhythmic activity. A privileged role for individual beta cells in orchestrating theseresponses has long-been suspected, but not directly demonstrated. We show here that the beta cellpopulation in situ is operationally heterogeneous. Mapping of islet functional architecturerevealed the presence of hub cells with pacemaker properties, which remain stable over recordingperiods of 2-3 hours. Using a dual optogenetic/photopharmacological strategy, silencing of hubsabolished coordinated islet responses to glucose, whereas specific stimulation restoredcommunication patterns. Hubs were metabolically-adapted and targeted by both proinflammatoryand glucolipotoxic insults to induce widespread beta cell dysfunction. Thus, theislet is wired by hubs, whose failure may contribute to type 2 diabetes mellitus.
AU  - Johnston,NR
AU  - Mitchell,RK
AU  - Haythorne,E
AU  - Pessoa,MP
AU  - Semplici,F
AU  - Ferrer,J
AU  - Piemonti,L
AU  - Marchetti,P
AU  - Bosco,D
AU  - Bugliani,M
AU  - Berishvilli,E
AU  - Duncanson,P
AU  - Watkinson,M
AU  - Broichhagen,J
AU  - Trauner,D
AU  - Rutter,GA
AU  - Hodson,DA
DO  - 10.1016/j.cmet.2016.06.020
EP  - 401
PY  - 2016///
SN  - 1932-7420
SP  - 389
TI  - Beta cell hubs dictate pancreatic islet responses to glucose
T2  - Cell Metabolism
UR  - http://dx.doi.org/10.1016/j.cmet.2016.06.020
UR  - http://hdl.handle.net/10044/1/34292
VL  - 24
ER  - 

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