Distribution of Free Amino Acids in Streptozotocin-Induced Diabetic Pregnant Rats, Their Placentae and Fetuses

Summary

Amino acid levels in the non-pregnant streptozotocin (STZ)-induced diabetic rat have been shown to be abnormal. Our preliminary studies showed that placental transport, fetal serum levels and tissue uptake of the non-metabolizable amino acid α-amino isobutyric acid (AIB) were decreased in STZ-diabetic pregnant rats. In the present experiments, amino acid concentrations were measured in maternal (MS) and fetal (FS) sera and placentae (PL) by high performance liquid chromatography (HPLC) after triple extraction in 80% ethanol. Control (C), STZ-diabetic (D) and insulin-treated diabetic (DI) animals were studied at 22 days gestation. Pregnant diabetic rats had low serum levels of Gln, Lys, and Ser and insulin treatment corrected Gln and Ser but not Lys levels. Branched-chain amino acids did not show the large elevation characteristic of the non-pregnant diabetic rat.

Placental levels of Tau, Gln, HPr, Thr and Lys were depressed in the diabetic animals and insulin treatment only partially improved these amino acid profiles. Placental amino acid levels did not always reflect maternal serum levels.

Serum levels of most amino acids were lower in the fetus of the diabetic rat than in the fetus of the control rat. The notable exception was Ala which was higher in the fetuses of the diabetic animals. Insulin treatment of the mother did not correct many of the fetal amino acid levels even though maternal and fetal serum glucose levels at the time of autopsy were normal. The ability to maintain normal serum levels of many amino acids is impaired in the fetus of the diabetic rat. This could result from decreased placental transport and/or increased fetal utilization. The fetus of the severely diabetic rat is not hyperinsulinemic. At present there is no reason to think that there is increased amino acid utilization. These results and previous studies utilizing the non-metabolizable amino acid AIB, suggest that placental transport of some amino acids may be compromised in the diabetic. The problem(s) may be at the placental-fetal interface rather than at the maternal-placental border for some amino acids, such as Trp. Insulin treatment of the diabetic mother, while apparently correcting mean blood glucose levels, does not correct all tissue and serum amino acid levels. Monitoring serum amino acid levels in pregnant diabetic women may aid in the evaluation of the therapeutic control of diabetes.

Key words

Streptozotocin - Maternal Diabetes - Amino Acid Transport - Free Amino Acids - Pregnant Rats