The purpose of this project is to test the hypothesis that maternal and fetal glucose supplies to the placenta regulate placental oxidative and non-oxidative metabolism of carbon substrates. These studies are important because of the essential role of the placenta in nutritive exchange between the mother and fetus, the remarkably high oxygen and substrate consumption rates of the placenta, and the major quantitative contribution of glucose to placental carbon substrate utilization. Studies will be conducted in pregnant sheep over the second half of gestation using chronically catheterized preparations during short and long-term experiments.
Two specific aims will be addressed: 1) to test in vivo the hypothesis that glucose supply to the placenta regulates placental glucose consumption, the production of other carbon compounds, and placental carbon accretion; 2) to test in vivo the hypothesis that glucose supply to the placenta regulates placental glucose oxidation and the oxidation of other carbon compounds. In vivo studies will use Fick principle, radioactive and stable isotopic tracer, and glucose/insulin clamp techniques to quantify net fluxes of substrates and substrate interconversions as regulated by placental glucose supply and insulin concentrations in maternal and fetal circulations. Because variation in maternal (and thus fetal) plasma glucose concentration in pregnancy, particularly in pathologic states such as starvation, fasting, and especially diabetes mellitus, are frequent and often extreme, understanding of the effect of glycemia and thus placental glucose supply on placental metabolic function is essential for determining how the placenta provides for fetal nutritional needs, fetal metabolism and growth, and fetal well-being.
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