title: Angiotensin II type 2 receptor regulates the development of pancreatic endocrine cells in mouse embryos.
abstract: BACKGROUND
  We previously identified a local renin-angiotensin system (RAS) regulating the differentiation of an isolated population of human pancreatic progenitor cells. Major RAS components that regulate organogenesis have been also described in embryos; however, it is not known whether a local RAS is present in the fetal pancreas. We now hypothesize that angiotensin II type 1 (AT1 ) and type 2 (AT2 ) receptors are expressed in mouse embryonic pancreas and involved in regulating endocrine cell development.
  
  
  RESULTS
  Differential expression of AT1 and AT2 receptors was observed in the mouse pancreata in late embryogenesis. Systemic AT2 , but not AT1 , receptor blockade during the second transition in pancreatic development (from embryonic day 12.0 onward) reduced the β-cell to α-cell ratio of the neonate islets, impaired their insulin secretory function and the glucose tolerance of the pups. Studies with pancreas explants ex vivo revealed regulation by AT2 receptors of the differentiation of pancreatic progenitors into insulin-producing cells and of the proliferation of the differentiated cell, actions that did not result from reduced angiogenesis as a secondary effect of AT2 receptor antagonism.
  
  
  CONCLUSIONS
  These data revealed an AT2 receptor-mediated mechanism regulating pancreatic endocrine cell development in vivo.
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Kwan Keung
authors.initials: KK
authors.lastname: Leung
authors.forename: Juan
authors.initials: J
authors.lastname: Liang
authors.forename: Shuiling
authors.initials: S
authors.lastname: Zhao
authors.forename: Wood Yee
authors.initials: WY
authors.lastname: Chan
authors.forename: Po Sing
authors.initials: PS
authors.lastname: Leung
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D005951:Glucose Tolerance Test; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D046790:Pancreas, Exocrine / Q000166:cytology / Q000196:embryology; D044140:Receptor, Angiotensin, Type 1 / Q000096:biosynthesis; D044139:Receptor, Angiotensin, Type 2 / Q000096:biosynthesis*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2
keywords: fetal pancreas; insulin; islet; renin-angiotensin system