EphA-Ephrin-A-Mediated β Cell Communication Regulates Insulin Secretion from Pancreatic Islets

Irena Konstantinova, Ganka Nikolova, Mica Ohara-Imaizumi, Paolo Meda, Tomáš Kučera, Konstantinos Zarbalis, Wolfgang Wurst, Shinya Nagamatsu, Eckhard Lammert

Research output: Contribution to journalArticle

217 Scopus citations

Abstract

In vertebrates, β cells are aggregated in the form of pancreatic islets. Within these islets, communication between β cells inhibits basal insulin secretion and enhances glucose-stimulated insulin secretion, thus contributing to glucose homeostasis during fasting and feeding. In the search for the underlying molecular mechanism, we have discovered that β cells communicate via ephrin-As and EphAs. We provide evidence that ephrin-A5 is required for glucose-stimulated insulin secretion. We further show that EphA-ephrin-A-mediated β cell communication is bidirectional: EphA forward signaling inhibits insulin secretion, whereas ephrin-A reverse signaling stimulates insulin secretion. EphA forward signaling is downregulated in response to glucose, which indicates that, under basal conditions, β cells use EphA forward signaling to suppress insulin secretion and that, under stimulatory conditions, they shift to ephrin-A reverse signaling to enhance insulin secretion. Thus, we explain how β cell communication in pancreatic islets conversely affects basal and glucose-stimulated insulin secretion to improve glucose homeostasis.

Original languageEnglish (US)
Pages (from-to)359-370
Number of pages12
JournalCell
Volume129
Issue number2
DOIs
StatePublished - Apr 20 2007
Externally publishedYes

Keywords

  • CELLBIO
  • HUMDISEASE

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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    Konstantinova, I., Nikolova, G., Ohara-Imaizumi, M., Meda, P., Kučera, T., Zarbalis, K., Wurst, W., Nagamatsu, S., & Lammert, E. (2007). EphA-Ephrin-A-Mediated β Cell Communication Regulates Insulin Secretion from Pancreatic Islets. Cell, 129(2), 359-370. https://doi.org/10.1016/j.cell.2007.02.044