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.
Address correspondence and reprint requests to Raphael Scharfmann, INSERM U457, Hospital R. Debré, Paris, France. E-mail:.
Received for publication 18 June 2002 and accepted in revised form 23 September 2002.
HBSS, Hanks balanced salt solution; IBMX, 3-isobutyl-1-methylxanthine; PACAP, pituitary adenylate cyclase-activating polypeptide; TGF, transforming growth factor; TUNEL, Tdl-mediated dUTP nick-end labeling; VIP, vasoactive intestinal peptide.