The objective of the proposed studies is to quantify the changes in maternal glucose and amino acid metabolism as they relate to fetal growth. It is proposed that the adaptation in the maternal metabolism during pregnancy is aimed at providing glucose for energy metabolism and amino acids for growth of the fetus and that alterations in these processes can impair fetal growth and well being. In addition, previous data from our studies show that liver is the key target organ which undergoes major pregnancy related metabolic alterations responsible for providing glucose and amino acids to the fetus and that synthesis of non- essential amino acids plays an important role in this process. The proposed studies are aimed at quantifying the changes in maternal hepatic glucose and amino acid metabolism with advancing gestation. A novel stable isotopic isotopomer analytic approach will be applied to quantify hepatic gluconeogenesis and its regulation. The kinetics of serine metabolism will be measured during fasting and in response to feeding, and the relation between maternal nd fetal serine pool documented at term gestation. It is hypothesized that the macrosomia in diabetic pregnancy may be related to the higher turnover rate of non- essential amino acid, and that intrauterine growth retardation may be related to limitations in both glucose and amino acids. Finally, the mechanistic question, specifically the role of insulin and HPL and fetal growth in these adaptive responses will be examined in animal models (Projects IV & V). It is anticipated that these studies will help define key metabolic processes in the mother that could be related to fetal growth and later help in the development of therapeutic interventions.
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