Chronic anemic hypoxemia increases plasma glucagon and hepatic PCK1 mRNA in late-gestation fetal sheep

Christine Culpepper, Stephanie R. Wesolowski, Joshua Benjamin, Jennifer L. Bruce, Laura D. Brown, Sonnet Jonker, Randall B. Wilkening, William W. Hay, Paul J. Rozance

    Research output: Contribution to journalArticle

    6 Citations (Scopus)

    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.

    Original languageEnglish (US)
    Pages (from-to)R200-R208
    JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
    Volume311
    Issue number1
    DOIs
    StatePublished - Jul 1 2016

    Fingerprint

    Glucagon
    Sheep
    Pregnancy
    Messenger RNA
    Fetus
    Liver
    Glucose
    Oxygen
    Hydrocortisone
    Liver Glycogen
    Hypoxia
    Hematocrit
    Hypoglycemia
    Hepatocytes
    Parturition
    Growth

    Keywords

    • Glucose
    • Glycogen
    • Hepatocyte
    • Oxygen
    • PEPCK

    ASJC Scopus subject areas

    • Physiology
    • Medicine(all)
    • Physiology (medical)

    Cite this

    Chronic anemic hypoxemia increases plasma glucagon and hepatic PCK1 mRNA in late-gestation fetal sheep. / Culpepper, Christine; Wesolowski, Stephanie R.; Benjamin, Joshua; Bruce, Jennifer L.; Brown, Laura D.; Jonker, Sonnet; Wilkening, Randall B.; Hay, William W.; Rozance, Paul J.

    In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 311, No. 1, 01.07.2016, p. R200-R208.

    Research output: Contribution to journalArticle

    Culpepper, Christine ; Wesolowski, Stephanie R. ; Benjamin, Joshua ; Bruce, Jennifer L. ; Brown, Laura D. ; Jonker, Sonnet ; Wilkening, Randall B. ; Hay, William W. ; Rozance, Paul J. / Chronic anemic hypoxemia increases plasma glucagon and hepatic PCK1 mRNA in late-gestation fetal sheep. In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology. 2016 ; Vol. 311, No. 1. pp. R200-R208.
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    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.",
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    AU - Brown, Laura D.

    AU - Jonker, Sonnet

    AU - Wilkening, Randall B.

    AU - Hay, William W.

    AU - Rozance, Paul J.

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    AB - 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.

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