title: Adrenal Demedullation and Oxygen Supplementation Independently Increase Glucose-Stimulated Insulin Concentrations in Fetal Sheep With Intrauterine Growth Restriction.
abstract: In pregnancies complicated by placental insufficiency and intrauterine growth restriction (IUGR), fetal glucose and oxygen concentrations are reduced, whereas plasma norepinephrine and epinephrine concentrations are elevated throughout the final third of gestation. Here we study the effects of chronic hypoxemia and hypercatecholaminemia on β-cell function in fetal sheep with placental insufficiency-induced IUGR that is produced by maternal hyperthermia. IUGR and control fetuses underwent a sham (intact) or bilateral adrenal demedullation (AD) surgical procedure at 0.65 gestation. As expected, AD-IUGR fetuses had lower norepinephrine concentrations than intact-IUGR fetuses despite being hypoxemic and hypoglycemic. Placental insufficiency reduced fetal weights, but the severity of IUGR was less with AD. Although basal plasma insulin concentrations were lower in intact-IUGR and AD-IUGR fetuses compared with intact-controls, glucose-stimulated insulin concentrations were greater in AD-IUGR fetuses compared with intact-IUGR fetuses. Interestingly, AD-controls had lower glucose- and arginine-stimulated insulin concentrations than intact-controls, but AD-IUGR and AD-control insulin responses were not different. To investigate chronic hypoxemia in the IUGR fetus, arterial oxygen tension was increased to normal levels by increasing the maternal inspired oxygen fraction. Oxygenation of IUGR fetuses enhanced glucose-stimulated insulin concentrations 3.3-fold in intact-IUGR and 1.7-fold in AD-IUGR fetuses but did not lower norepinephrine and epinephrine concentrations. Together these findings show that chronic hypoxemia and hypercatecholaminemia have distinct but complementary roles in the suppression of β-cell responsiveness in IUGR fetuses.
authors.affiliation: School of Animal and Comparative Biomedical Sciences, The University of Arizona, Tucson, Arizona 85719.
authors.forename: Antoni R
authors.initials: AR
authors.lastname: Macko
authors.affiliation: School of Animal and Comparative Biomedical Sciences, The University of Arizona, Tucson, Arizona 85719.
authors.forename: Dustin T
authors.initials: DT
authors.lastname: Yates
authors.affiliation: School of Animal and Comparative Biomedical Sciences, The University of Arizona, Tucson, Arizona 85719.
authors.forename: Xiaochuan
authors.initials: X
authors.lastname: Chen
authors.affiliation: School of Animal and Comparative Biomedical Sciences, The University of Arizona, Tucson, Arizona 85719.
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Shelton
authors.affiliation: School of Animal and Comparative Biomedical Sciences, The University of Arizona, Tucson, Arizona 85719.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Kelly
authors.affiliation: School of Animal and Comparative Biomedical Sciences, The University of Arizona, Tucson, Arizona 85719.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Davis
authors.affiliation: School of Animal and Comparative Biomedical Sciences, The University of Arizona, Tucson, Arizona 85719.
authors.forename: Leticia E
authors.initials: LE
authors.lastname: Camacho
authors.affiliation: School of Animal and Comparative Biomedical Sciences, The University of Arizona, Tucson, Arizona 85719.
authors.forename: Miranda J
authors.initials: MJ
authors.lastname: Anderson
authors.affiliation: School of Animal and Comparative Biomedical Sciences, The University of Arizona, Tucson, Arizona 85719.
authors.forename: Sean W
authors.initials: SW
authors.lastname: Limesand
mesh_terms: D000313:Adrenal Medulla / Q000601:surgery*; D000818:Animals; D005260:Female; D005317:Fetal Growth Retardation / Q000097:blood*; D020567:Fetal Weight / Q000187:drug effects; D005333:Fetus / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D010100:Oxygen / Q000494:pharmacology; D010102:Oxygen Inhalation Therapy; D010927:Placental Insufficiency / Q000097:blood*; D011247:Pregnancy; D012756:Sheep
chemical_list: D007328:Insulin; D005947:Glucose; D010100:Oxygen