title: Chronic anemic hypoxemia attenuates glucose-stimulated insulin secretion in fetal sheep.
abstract: Fetal insulin secretion is inhibited by acute hypoxemia. The relationship between prolonged hypoxemia and insulin secretion, however, is less well defined. To test the hypothesis that prolonged fetal hypoxemia impairs insulin secretion, studies were performed in sheep fetuses that were bled to anemic conditions for 9 ± 0 days (anemic,n= 19) and compared with control fetuses (n= 15). Arterial hematocrit and oxygen content were 34% and 52% lower, respectively, in anemic vs. control fetuses (P< 0.0001). Plasma glucose concentrations were 21% higher in the anemic group (P< 0.05). Plasma norepinephrine and cortisol concentrations increased 70% in the anemic group (P< 0.05). Glucose-, arginine-, and leucine-stimulated insulin secretion all were lower (P< 0.05) in anemic fetuses. No differences in pancreatic islet size or β-cell mass were found. In vitro, isolated islets from anemic fetuses secreted insulin in response to glucose and leucine as well as control fetal islets. These findings indicate a functional islet defect in anemic fetuses, which likely involves direct effects of low oxygen and/or increased norepinephrine on insulin release. In pregnancies complicated by chronic fetal hypoxemia, increasing fetal oxygen concentrations may improve insulin secretion.
authors.affiliation: Perinatal Research Center, Department of Pediatrics, University of Colorado Denver School of Medicine, Aurora, Colorado.
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Benjamin
authors.affiliation: Perinatal Research Center, Department of Pediatrics, University of Colorado Denver School of Medicine, Aurora, Colorado.
authors.forename: Christine B
authors.initials: CB
authors.lastname: Culpepper
authors.affiliation: Perinatal Research Center, Department of Pediatrics, University of Colorado Denver School of Medicine, Aurora, Colorado.|Center for Women's Health Research, University of Colorado Denver School of Medicine, Aurora, Colorado.
authors.forename: Laura D
authors.initials: LD
authors.lastname: Brown
authors.affiliation: Perinatal Research Center, Department of Pediatrics, University of Colorado Denver School of Medicine, Aurora, Colorado.|Center for Women's Health Research, University of Colorado Denver School of Medicine, Aurora, Colorado.
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Wesolowski
authors.affiliation: Knight Cardiovascular Institute Center for Developmental Health, Oregon Health & Science University, Portland, Oregon; and.
authors.forename: Sonnet S
authors.identifier: 0000-0002-1097-2562
authors.initials: SS
authors.lastname: Jonker
authors.affiliation: School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, Arizona.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Davis
authors.affiliation: School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, Arizona.
authors.forename: Sean W
authors.initials: SW
authors.lastname: Limesand
authors.affiliation: Perinatal Research Center, Department of Pediatrics, University of Colorado Denver School of Medicine, Aurora, Colorado.
authors.forename: Randall B
authors.initials: RB
authors.lastname: Wilkening
authors.affiliation: Perinatal Research Center, Department of Pediatrics, University of Colorado Denver School of Medicine, Aurora, Colorado.
authors.forename: William W
authors.initials: WW
authors.lastname: Hay
authors.affiliation: Perinatal Research Center, Department of Pediatrics, University of Colorado Denver School of Medicine, Aurora, Colorado; Paul.Rozance@ucdenver.edu.|Center for Women's Health Research, University of Colorado Denver School of Medicine, Aurora, Colorado.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Rozance
mesh_terms: D000740:Anemia / Q000196:embryology / Q000378:metabolism; D000818:Animals; D002908:Chronic Disease; D015536:Down-Regulation; D005260:Female; D005311:Fetal Hypoxia / Q000196:embryology* / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000196:embryology* / Q000378:metabolism*; D008297:Male; D012756:Sheep
chemical_list: D007328:Insulin; D005947:Glucose
keywords: fetus; islet; oxygen; pancreas; β-cell