Beta Cell Hubs Dictate Pancreatic Islet Responses to Glucose

Watkinson

Abstract

The arrangement of ß cells within islets of Langerhans is critical for insulin release through the generation of rhythmic activity. A privileged role for individual ß cells in orchestrating these responses has long been suspected, but not directly demonstrated. We show here that the ß 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 ß cell dysfunction. Thus, the islet is wired by hubs, whose failure may contribute to type 2 diabetes mellitus.

• Acceptance Date: Jun 23, 2016
• Publication Date: Jul 21, 2016
• Journal: Cell Metabolism
• Print ISSN: 1550-4131
• Publisher: Elsevier
• Pages: 389 - 401
• DOI: https://doi.org/10.1016/j.cmet.2016.06.020
• Keywords: islets, insulin, ß cells, diabetes, optogenetics, imaging
• Publisher URL: https://doi.org/10.1016/j.cmet.2016.06.020