Hypothesis: Nitrogen accretion in maternal (and fetal) compartment involves down-regulation of transaminases, resulting in decreased turnover (synthesis) of non-essential amino acids such as glutamine, and that the down-regulation is easily perturbed by decreased insulin availability (or action) in gestational diabetes mellitus.
Specific Aims : 1) Quantify whole body kinetics of glutamine in pregnancy and its release from skeletal muscle. 2) Quantify the contribution of branched chain amino acid N to glutamine and alanine N in the third trimester of pregnancy.
These specific aims will be investigated via 2 sub-studies, as described below: Study 1 - Glutamine Kinetics in Pregnancy The rate of appearance of glutamine in the plasma will be quantified using L[5-15N]glutamine tracer as a prime constant rate infusion method. Simultaneously, the forearm balance of glutamine will be quantified by measuring the artery-vein difference in concentration across the forearm in combination with measurements of tracer enrichments and measurements of blood flow. In addition, the rate of proteolysis in the whole body will be quantified using [2H5]phenylalanine tracer. The effect of nutrient intake will be examined by administering a liquid diet. Study 2 - Contribution of branched-chain amino N to glutamine and alanine N in pregnancy These studies will be performed on five normal pregnant and five non-pregnant women. The pregnant women will be studied in the third trimester of pregnancy only - a time of maximal change in leucine N kinetics. The subjects will be infused on consecutive days with either [15N]leucine or [15N]alanine or [15N]glutamine as prime constant rate infusion. The transfer of 15N from leucine to alanine or glutamine will be calculated from their respective turnover rates and by comparing the enrichments of respective pools of the precursor and product. Four groups of subjects are required for the proposed studies; normal non-pregnant adults, normal pregnant women at different gestations, gestationally diabetic pregnant women and mothers with intrauterine growth retarded fetuses. Eight subjects have been studied thus far. The plasma samples are being analyzed, however no data are available to report at this time.
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