title: Pancreatic islet hepatocyte growth factor and vascular endothelial growth factor A signaling in growth restricted fetuses.
abstract: Placental insufficiency leads to intrauterine growth restriction (IUGR) and a lifelong risk of developing type 2 diabetes. Impaired islet development in the growth restricted fetus, including decreased β-cell replication, mass, and insulin secretion, is strongly implicated in the pathogenesis of later life type 2 diabetes. Currently, standard medical management of a woman with a pregnancy complicated by placental insufficiency and fetal IUGR is increased fetal surveillance and indicated preterm delivery. This leads to the dual complications of IUGR and preterm birth - both of which may increase the lifelong risk for type 2 diabetes. In order to develop therapeutic interventions in IUGR pregnancies complicated by placental insufficiency and decrease the risk of later development of type 2 diabetes in the offspring, the mechanisms responsible for impaired islet development in these cases must be determined. This review focuses on current investigations testing the hypothesis that decreased nutrient supply to the IUGR fetus inhibits an intra-islet hepatocyte growth factor - vascular endothelial growth factor A (HGF - VEGFA) feed forward signaling pathway and that this is responsible for developmental islet defects.
authors.affiliation: Perinatal Research Center, University of Colorado Denver School of Medicine, Department of Pediatrics, USA. Electronic address: Paul.Rozance@ucdenver.edu.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Rozance
authors.affiliation: Perinatal Research Center, University of Colorado Denver School of Medicine, Department of Pediatrics, USA.
authors.forename: William W
authors.initials: WW
authors.lastname: Hay
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000196:embryology* / Q000453:epidemiology*; D005260:Female; D005317:Fetal Growth Retardation / Q000503:physiopathology*; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D015995:Prevalence; D012307:Risk Factors; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D017228:Hepatocyte Growth Factor
keywords: Hepatocyte growth factor; Insulin; Intrauterine growth restriction; Pancreatic islet; Pregnancy; Vascular endothelial cell growth factor
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