Format

Send to

Choose Destination
Cell Metab. 2016 Sep 13;24(3):389-401. doi: 10.1016/j.cmet.2016.06.020. Epub 2016 Jul 21.

Beta Cell Hubs Dictate Pancreatic Islet Responses to Glucose.

Author information

1
Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College London, London W12 0NN, UK.
2
Beta Cell Genome Regulation Lab, Department of Medicine, Imperial College London, London W12 0NN, UK.
3
Diabetes Research Institute (HSR-DRI), San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy.
4
Department of Clinical and Experimental Medicine, Islet Cell Laboratory, University of Pisa, 56126 Pisa, Italy.
5
Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals and University of Geneva, 1205 Geneva, Switzerland.
6
School of Biological and Chemical Sciences, Queen Mary University of London, Mile End Road, London E1 4NS, UK.
7
Department of Chemistry, Ludwig-Maximilians-Universität München, and Munich Center for Integrated Protein Science, Butenandtstrasse 5-13, 81377 München, Germany.
8
Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College London, London W12 0NN, UK. Electronic address: g.rutter@imperial.ac.uk.
9
Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College London, London W12 0NN, UK; Institute of Metabolism and Systems Research (IMSR) and Centre of Membrane Proteins and Receptors (COMPARE), University of Birmingham, Birmingham B15 2TT, UK; Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham B15 2TH, UK. Electronic address: d.hodson@bham.ac.uk.

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.

KEYWORDS:

diabetes; imaging; insulin; islets; optogenetics; β cells

PMID:
27452146
PMCID:
PMC5031557
DOI:
10.1016/j.cmet.2016.06.020
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center