EphA-Ephrin-A-mediated beta cell communication regulates insulin secretion from pancreatic islets.
In vertebrates, beta cells are aggregated in the form of pancreatic islets. Within these islets, communication between beta 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 beta 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 beta 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, beta 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 beta cell communication in pancreatic islets conversely affects basal and glucose-stimulated insulin secretion to improve glucose homeostasis.
Konstantinova
Irena
I
Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
Nikolova
Ganka
G
Ohara-Imaizumi
Mica
M
Meda
Paolo
P
Kucera
Tomás
T
Zarbalis
Konstantinos
K
Wurst
Wolfgang
W
Nagamatsu
Shinya
S
Lammert
Eckhard
E
D000818:Animals; D002450:Cell Communication; D002460:Cell Line; D036386:Ephrin-A5 / Q000378:metabolism; D036342:Ephrins / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D010766:Phosphorylation; D036081:Receptors, Eph Family / Q000378:metabolism*; D015398:Signal Transduction
D036386:Ephrin-A5; D036342:Ephrins; D007328:Insulin; D036081:Receptors, Eph Family; D005947:Glucose