Beta Cell Hubs Dictate Pancreatic Islet Responses to Glucose

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


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.

MeSH terms

  • Animals
  • Calcium Signaling / drug effects
  • Calcium Signaling / radiation effects
  • Cell Differentiation / drug effects
  • Computer Systems
  • Diabetes Mellitus / pathology
  • Glucose / pharmacology*
  • Homeostasis / drug effects
  • Homeostasis / radiation effects
  • Humans
  • Insulin / metabolism
  • Insulin Secretion
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / metabolism*
  • Light
  • Lipids / toxicity
  • Metabolome / drug effects
  • Metabolomics
  • Mice
  • Optical Phenomena
  • Phenotype
  • Species Specificity


  • Insulin
  • Lipids
  • Glucose