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.
Original language | English |
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Pages (from-to) | 389-401 |
Number of pages | 13 |
Journal | Cell Metabolism |
Volume | 24 |
Issue number | 3 |
Early online date | 21 Jul 2016 |
DOIs | |
Publication status | Published - 13 Sept 2016 |
Keywords
- islets
- insulin
- β cells
- diabetes
- optogenetics
- imaging