Culpepper Christine, Wesolowski Stephanie R, Benjamin Joshua, Bruce Jennifer L, Brown Laura D, Jonker Sonnet S, Wilkening Randall B, Hay William W, Rozance Paul J
Perinatal Research Center, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado;
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.
Am J Physiol Regul Integr Comp Physiol. 2016 Jul 1;311(1):R200-8. doi: 10.1152/ajpregu.00037.2016. Epub 2016 May 11.
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.
肝葡萄糖生成（HGP）通常在出生前就开始了。长时间的胎儿低血糖、子宫内生长受限和急性低氧血症会导致胎儿HGP提前激活。为了验证长时间低氧血症会增加调节HGP的因子这一假设，对失血致贫血状态的胎儿（贫血组：n = 11）进行了为期8.9±0.4天的研究，并与对照胎儿（n = 7）进行比较。与对照组相比，贫血胎儿的动脉血细胞比容和氧含量分别降低了32%和50%（P < 0.005）。贫血组的动脉血浆葡萄糖水平高15%（P < 0.05）。贫血组中磷酸烯醇式丙酮酸羧激酶（PCK1）的肝mRNA表达高出两倍（P < 0.05）。与对照组相比，贫血胎儿的动脉血浆胰高血糖素浓度高70%（P < 0.05），且与肝PCK1 mRNA表达呈正相关（P < 0.05）。贫血胎儿的动脉血浆皮质醇浓度增加了90%（P < 0.05），但胎儿皮质醇浓度与肝PCK1 mRNA表达无关。与对照胎儿相比，贫血胎儿的肝糖原含量低30%（P < 0.05），且与胎儿动脉血浆胰高血糖素浓度呈负相关。在分离的原代胎儿绵羊肝细胞中，与正常氧（21%）孵育相比，低氧（3%）孵育使PCK1 mRNA增加了三倍。这些结果共同表明，在慢性胎儿贫血性低氧血症期间，胰高血糖素和PCK1可能增强胎儿HGP。
