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Beta cell hubs dictate pancreatic islet responses to glucose

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CELL-METABOLISM-D-15-01094_R2.pdfAccepted version3.16 MBAdobe PDFView/Open
1-s2.0-S1550413116303060-main.pdfPublished version3.95 MBAdobe PDFView/Open
Title: Beta cell hubs dictate pancreatic islet responses to glucose
Authors: Johnston, NR
Mitchell, RK
Haythorne, E
Pessoa, MP
Semplici, F
Ferrer, J
Piemonti, L
Marchetti, P
Bosco, D
Bugliani, M
Berishvilli, E
Duncanson, P
Watkinson, M
Broichhagen, J
Trauner, D
Rutter, GA
Hodson, DA
Item Type: Journal Article
Abstract: The arrangement of beta cells within islets of Langerhans is critical for insulin release through the generation of rhythmic activity. A privileged role for individual beta cells in orchestrating these responses has long-been suspected, but not directly demonstrated. We show here that the beta 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 2-3 hours. 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 proinflammatory and glucolipotoxic insults to induce widespread beta cell dysfunction. Thus, the islet is wired by hubs, whose failure may contribute to type 2 diabetes mellitus.
Issue Date: 13-Sep-2016
Date of Acceptance: 13-Jun-2016
URI: http://hdl.handle.net/10044/1/34292
DOI: https://dx.doi.org/10.1016/j.cmet.2016.06.020
ISSN: 1932-7420
Publisher: Elsevier (Cell Press)
Start Page: 389
End Page: 401
Journal / Book Title: Cell Metabolism
Volume: 24
Issue: 3
Copyright Statement: © 2016 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
Sponsor/Funder: Commission of the European Communities
The Royal Society
Medical Research Council (MRC)
Diabetes UK
Wellcome Trust
Biotechnology and Biological Sciences Research Council (BBSRC)
Diabetes UK
Medical Research Council (MRC)
Wellcome Trust
Medical Research Council (MRC)
Funder's Grant Number: 115005
WM100078
MR/K001981/1
12/0004601
098424/Z/12/ZR
BB/J015873/1
15821
MR/L02036X/1
105603/Z/14/Z
R26199/CN001
Keywords: diabetes
imaging
insulin
islets
optogenetics
β cells
Endocrinology & Metabolism
0601 Biochemistry And Cell Biology
1101 Medical Biochemistry And Metabolomics
Publication Status: Published
Appears in Collections:Department of Medicine
Faculty of Medicine



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