TY - JOUR
T1 - Insulin-like growth factor and fibroblast growth factor expression profiles in growth-restricted fetal sheep pancreas
AU - Chen, Xiaochuan
AU - Rozance, Paul J.
AU - Hay, William W.
AU - Limesand, Sean W.
N1 - Funding Information:
This work was supported by grants from the National Institutes of Health (DK084842, SWL, Principle Investigator and HD42815, WWH Jr, Principle Investigator). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We would like to thank Miranda Anderson and Megan Wyckoff for their technical assistance with this work.
PY - 2012/5
Y1 - 2012/5
N2 - 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.
AB - 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.
KW - Fetal programming
KW - Insulin
KW - Intrauterine growth restriction
KW - Islets of Langerhans
KW - Placental insufficiency
KW - β-cell
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U2 - 10.1258/ebm.2012.011375
DO - 10.1258/ebm.2012.011375
M3 - Article
C2 - 22581814
AN - SCOPUS:84862016395
SN - 1535-3702
VL - 237
SP - 524
EP - 529
JO - Experimental Biology and Medicine
JF - Experimental Biology and Medicine
IS - 5
ER -