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Diabetes. 2015 Feb;64(2):555-64. doi: 10.2337/db14-0462. Epub 2014 Sep 23.

Placental insufficiency decreases pancreatic vascularity and disrupts hepatocyte growth factor signaling in the pancreatic islet endothelial cell in fetal sheep.

Author information

1
Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO Perinatal Research Center, University of Colorado School of Medicine, Aurora, CO paul.rozance@ucdenver.edu.
2
School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ.
3
Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO Perinatal Research Center, University of Colorado School of Medicine, Aurora, CO.
4
Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO Pediatric Heart Lung Center, University of Colorado School of Medicine, Aurora, CO.

Abstract

Hepatocyte growth factor (HGF) and vascular endothelial growth factor A (VEGFA) are paracrine hormones that mediate communication between pancreatic islet endothelial cells (ECs) and β-cells. Our objective was to determine the impact of intrauterine growth restriction (IUGR) on pancreatic vascularity and paracrine signaling between the EC and β-cell. Vessel density was less in IUGR pancreata than in controls. HGF concentrations were also lower in islet EC-conditioned media (ECCM) from IUGR, and islets incubated with control islet ECCM responded by increasing insulin content, which was absent with IUGR ECCM. The effect of ECCM on islet insulin content was blocked with an inhibitory anti-HGF antibody. The HGF receptor was not different between control and IUGR islets, but VEGFA was lower and the high-affinity VEGF receptor was higher in IUGR islets and ECs, respectively. These findings show that paracrine actions from ECs increase islet insulin content, and in IUGR ECs, secretion of HGF was diminished. Given the potential feed-forward regulation of β-cell VEGFA and islet EC HGF, these two growth factors are highly integrated in normal pancreatic islet development, and this regulation is decreased in IUGR fetuses, resulting in lower pancreatic islet insulin concentrations and insulin secretion.

PMID:
25249573
PMCID:
PMC4303968
DOI:
10.2337/db14-0462
[Indexed for MEDLINE]
Free PMC Article

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