Relationship Between Maternal and Fetal Fuels and Placental Glucose Transfer in Rats with Maternal Diabetes of Varying Severity

Abstract

Gestational diabetes mellitus (GDM) is a nonhomogenous entity known to affect fetal development in different ways in both rats and human beings. The degree of severity of diabetes could affect the maternal-fetal transfer of metabolic fuels and consequently influence fetal development. To study this hypothesis, pregnant rats were made diabetic by streptozocin (STZ) treatment (45 mg/kg) at day 7 of gestation and were treated with different daily doses of insulin until the 20th day of gestation, when-they were killed and examined. Differences in plasma glucose levels in the groups studied were not accompanied by differences in plasma glycerol, β-hydroxybutyrate (β-OHB), or total amino acid levels in mothers or their fetuses. Fetal/maternal ratios of these circulating fuels were not modified by maternal diabetes, whereas the glucose level was enhanced in diabetic rats not treated with insulin. Placental glucose transfer was studied directly with a recently reported in situ experimental design and was found to increase linearly with maternal glycemia, independently of whether this was modified by insulin treatment or by acute intravenous (i.v.) infusion of glucose in normal animals. Lactate production by the fetal/placental unit decreased in proportion to the glucose level in the maternal circulation. The present data indicate that the diabetic condition of the mother rat does not modify the mechanisms of placental transfer of metabolic fuels to the fetus, and that the actual transfer is mainly dependent on the concentrations of these fuels in the maternal circulation. The limited capacity of the fetus to handle the great influx of glucose through the placenta of a highly hyperglycemic mother may aggravate the diabetic condition of the fetus, affecting its subsequent development.