Insulin-like growth factor and fibroblast growth factor expression profiles in growth-restricted fetal sheep pancreas

Xiaochuan Chen, Paul J. Rozance, William W. Hay, Sean W Limesand

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)524-529
Number of pages6
JournalExperimental Biology and Medicine
Volume237
Issue number5
DOIs
StatePublished - May 2012

Fingerprint

Fibroblast Growth Factors
Somatomedins
Fetal Development
Pancreas
Sheep
Insulin-Like Growth Factor Binding Protein 2
Messenger RNA
Homeobox Genes
Cell proliferation
Growth
Intercellular Signaling Peptides and Proteins
Fetus
Cell Proliferation
Placental Insufficiency
Insulin
Insulin-Like Growth Factor Binding Proteins
Insulin-Like Growth Factor II
Growth Factor Receptors
Insulin-Like Growth Factor I
Transcription Factors

Keywords

  • β-cell
  • Fetal programming
  • Insulin
  • Intrauterine growth restriction
  • Islets of Langerhans
  • Placental insufficiency

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Insulin-like growth factor and fibroblast growth factor expression profiles in growth-restricted fetal sheep pancreas. / Chen, Xiaochuan; Rozance, Paul J.; Hay, William W.; Limesand, Sean W.

In: Experimental Biology and Medicine, Vol. 237, No. 5, 05.2012, p. 524-529.

Research output: Contribution to journalArticle

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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.",
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