title: Insulin-like growth factor and fibroblast growth factor expression profiles in growth-restricted fetal sheep pancreas.
abstract: Placental insufficiency results in intrauterine growth restriction (IUGR), impaired fetal insulin secretion and less fetal pancreatic β-cell mass, partly due to lower β-cell proliferation rates. Insulin-like growth factors (IGFs) and fibroblast growth factors (FGFs) regulate fetal β-cell proliferation and pancreas development, along with transcription factors, such as pancreatic and duodenal homeobox 1 (PDX-1). We determined expression levels for these growth factors, their receptors and IGF binding proteins in ovine fetal pancreas and isolated islets. In the IUGR pancreas, relative mRNA expression levels of IGF-I, PDX-1, FGF7 and FGFR2IIIb were 64% (P < 0.01), 76% (P < 0.05), 76% (P < 0.05) and 52% (P < 0.01) lower, respectively, compared with control fetuses. Conversely, insulin-like growth factor binding protein 2 (IGFBP-2) mRNA and protein concentrations were 2.25- and 1.2-fold greater (P < 0.05) in the IUGR pancreas compared with controls. In isolated islets from IUGR fetuses, IGF-II and IGFBP-2 mRNA concentrations were 1.5- and 3.7-fold greater (P < 0.05), and insulin mRNA was 56% less (P < 0.05) than control islets. The growth factor expression profiles for IGF and FGF signaling pathways indicate that declines in β-cell mass are due to decreased growth factor signals for both pancreatic progenitor epithelial cell and mature β-cell replication.
authors.affiliation: Agricultural Research Complex, Department of Animal Sciences, University of Arizona, 4101 N Campbell Ave, Tucson, AZ 85719, USA.
authors.forename: Xiaochuan
authors.initials: X
authors.lastname: Chen
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Rozance
authors.forename: William W
authors.initials: WW
authors.lastname: Hay
authors.forename: Sean W
authors.initials: SW
authors.lastname: Limesand
mesh_terms: D000818:Animals; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism*; D005333:Fetus / Q000378:metabolism; D051523:Fibroblast Growth Factor 7 / Q000096:biosynthesis* / Q000235:genetics; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D007328:Insulin / Q000096:biosynthesis / Q000235:genetics; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000096:biosynthesis / Q000235:genetics; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000235:genetics; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007515:Islets of Langerhans / Q000196:embryology / Q000378:metabolism; D010179:Pancreas / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism*; D010927:Placental Insufficiency / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000096:biosynthesis / Q000235:genetics; D034561:Sheep, Domestic; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics
chemical_list: D018398:Homeodomain Proteins; D007328:Insulin; D018971:Insulin-Like Growth Factor Binding Protein 2; D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D051523:Fibroblast Growth Factor 7; D007334:Insulin-Like Growth Factor I; D051497:Receptor, Fibroblast Growth Factor, Type 2