During maternal fasting, the ovine fetus catabolizes amino acids at the expense of tissue accretion to a greater extent than when the ewe is well fed, thereby compromising fetal growth. Characteristically, fasting also results in fetal hypoglycemia, hypoinsulinemia, and generalized hyperaminoacidemia. The increase in arterial concentration of the branched chain amino acids is especially pronounced. It is not known what factors regulate the flow of amino acids within the fetus to either tissue accretion or catabolism.
The aims of the proposed project are to determine the independent effect of arterial glucose concentration, insulin concentration, and branched chain amino acid (BCAA) concentration on fetal amino acid kinetics. Specifically, leucine will be studied, because fasting, as well as insulin and glucose concentrations are known to influence its metabolism in the mammalian fetus as well as in postnatal animals. The chronic ovine fetal preparation will be utilized. 15N-1-13C- leucine will be infused into the fetus, with leucine kinetics determined at steady state. A series of four experiments will be carried out as follows: 1.) Effect of glucose concentration on BCAA kinetics. Glucose will be infused into the fetus at varying rates, with leucine kinetics determined at each rate. 2.) Effect of varying glucose infusions with constant insulin concentration. Again glucose will be infused into the fetus, but fetal insulin secretion will be inhibited by somatostatin infusion, followed by constant insulin replacement. 3.) Effect of varying insulin concentrations at constant glucose concentration. Fetal arterial glucose concentrations will be """"""""clamped"""""""" at predetermined concentrations, and insulin concentrations altered by exogenous infusion. 4.) Effect of branched chain amino acid infusion. Branched chain amino acid mixture will be infused into the fetus, with and without glucose and insulin concentrations held constant. In summary, the independent effects of glucose, insulin, and branched chain amino acid concentrations on fetal leucine utilization will be examined. This information will advance our understanding of the modulations of fetal growth which occur with maternal undernutrition, as well as in pathologic states which result in fetal undernutrition. Information gained will be valuable in determining optimal nutritional support of mothers or fetuses in situations where aberrant fetal growth is detected.
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