Role for VPAC2 receptor-mediated signals in pancreas development.
Mature pancreatic cells develop from progenitors that proliferate and differentiate into endocrine and exocrine cells. This development is thought to be controlled by secreted soluble factors acting on their target cells after binding to membrane receptors. Here, we analyzed the impact on embryonic pancreatic development of ligands that bind to protein G-coupled receptors and increase cAMP accumulation. We found that embryonic pancreatic epithelial cells were sensitive to vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide. These factors generate signals after binding to the VPAC2 receptor, which is expressed by immature pancreatic epithelial cells between embryonic days 12 and 16. Finally, in vitro, VIP exposure increased the survival and proliferation of immature pancreatic cells, leading to an increase in the number of endocrine cells that will develop.
Rachdi
Latif
L
INSERM U457, Hospital R. Debré, Paris, France.
Marie
Jean-Claude
JC
Scharfmann
Raphael
R
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000242:Cyclic AMP / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D005314:Embryonic and Fetal Development / Q000187:drug effects / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D008024:Ligands; D009479:Neuropeptides / Q000008:administration & dosage / Q000494:pharmacology; D009924:Organ Culture Techniques; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D017208:Rats, Wistar; D018005:Receptors, Vasoactive Intestinal Peptide / Q000502:physiology*; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D015398:Signal Transduction / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000008:administration & dosage / Q000494:pharmacology
C495403:Adcyap1 protein, rat; D008024:Ligands; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D018005:Receptors, Vasoactive Intestinal Peptide; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP