title: Chronic anemic hypoxemia increases plasma glucagon and hepatic PCK1 mRNA in late-gestation fetal sheep.
abstract: Hepatic glucose production (HGP) normally begins just prior to birth. Prolonged fetal hypoglycemia, intrauterine growth restriction, and acute hypoxemia produce an early activation of fetal HGP. To test the hypothesis that prolonged hypoxemia increases factors which regulate HGP, studies were performed in fetuses that were bled to anemic conditions (anemic: n = 11) for 8.9 ± 0.4 days and compared with control fetuses (n = 7). Fetal arterial hematocrit and oxygen content were 32% and 50% lower, respectively, in anemic vs. controls (P < 0.005). Arterial plasma glucose was 15% higher in the anemic group (P < 0.05). Hepatic mRNA expression of phosphonenolpyruvate carboxykinase (PCK1) was twofold higher in the anemic group (P < 0.05). Arterial plasma glucagon concentrations were 70% higher in anemic fetuses compared with controls (P < 0.05), and they were positively associated with hepatic PCK1 mRNA expression (P < 0.05). Arterial plasma cortisol concentrations increased 90% in the anemic fetuses (P < 0.05), but fetal cortisol concentrations were not correlated with hepatic PCK1 mRNA expression. Hepatic glycogen content was 30% lower in anemic vs. control fetuses (P < 0.05) and was inversely correlated with fetal arterial plasma glucagon concentrations. In isolated primary fetal sheep hepatocytes, incubation in low oxygen (3%) increased PCK1 mRNA threefold compared with incubation in normal oxygen (21%). Together, these results demonstrate that glucagon and PCK1 may potentiate fetal HGP during chronic fetal anemic hypoxemia.
authors.affiliation: Perinatal Research Center, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado;
authors.forename: Christine
authors.initials: C
authors.lastname: Culpepper
authors.affiliation: Perinatal Research Center, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado; Center for Women's Health Research, University of Colorado School of Medicine, Aurora, Colorado; and.
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Wesolowski
authors.affiliation: Perinatal Research Center, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado;
authors.forename: Joshua
authors.initials: J
authors.lastname: Benjamin
authors.affiliation: Perinatal Research Center, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado;
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Bruce
authors.affiliation: Perinatal Research Center, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado; Center for Women's Health Research, University of Colorado School of Medicine, Aurora, Colorado; and.
authors.forename: Laura D
authors.initials: LD
authors.lastname: Brown
authors.affiliation: Knight Cardiovascular Institute Center for Developmental Health, Oregon Health & Science University, Portland, Oregon.
authors.forename: Sonnet S
authors.identifier: 0000-0002-1097-2562
authors.initials: SS
authors.lastname: Jonker
authors.affiliation: Perinatal Research Center, Department of Pediatrics, University of Colorado 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 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 School of Medicine, Aurora, Colorado; Center for Women's Health Research, University of Colorado School of Medicine, Aurora, Colorado; and Paul.Rozance@ucdenver.edu.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Rozance
mesh_terms: D000740:Anemia / Q000378:metabolism*; D000818:Animals; D005260:Female; D005311:Fetal Hypoxia / Q000378:metabolism*; D005333:Fetus / Q000378:metabolism*; D005934:Glucagon / Q000097:blood*; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism; D006854:Hydrocortisone / Q000097:blood; D000860:Hypoxia / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D009929:Organ Size; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D012756:Sheep; D014470:Umbilical Cord
chemical_list: D012333:RNA, Messenger; D006003:Glycogen; D005934:Glucagon; D005952:Glucose-6-Phosphatase; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D006854:Hydrocortisone
keywords: PEPCK; glucose; glycogen; hepatocyte; oxygen