Effect of dexamethasone on fetal hepatic glutamine-glutamate exchange.
Intravenous infusion of dexamethasone (Dex) in the fetal lamb causes a two- to threefold increase in plasma glutamine and other glucogenic amino acids and a decrease of plasma glutamate to approximately one-third of normal. To explore the underlying mechanisms, hepatic amino acid uptake and conversion of L-[1-(13)C]glutamine to L-[1-(13)C]glutamate and (13)CO(2) were measured in six sheep fetuses before and in the last 2 h of a 26-h Dex infusion. Dex decreased hepatic glutamine and alanine uptakes (P < 0.01) and hepatic glutamate output (P < 0.001). Hepatic outputs of the glutamate (R(Glu,Gln)) and CO(2) formed from plasma glutamine decreased to 21 (P < 0.001) and 53% (P = 0.009) of control, respectively. R(Glu,Gln), expressed as a fraction of both outputs, decreased (P < 0.001) from 0.36 +/- 0.02 to 0.18 +/- 0.04. Hepatic glucose output remained virtually zero throughout the experiment. We conclude that Dex decreases fetal hepatic glutamate output by increasing the routing of glutamate carbon into the citric acid cycle and by decreasing the hepatic uptake of glucogenic amino acids.
Timmerman
M
M
Department of Obstetrics and Gynecology, Erasmus University, 3000 DR Rotterdam, The Netherlands.
Teng
C
C
Wilkening
R B
RB
Fennessey
P
P
Battaglia
F C
FC
Meschia
G
G
D000409:Alanine / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002247:Carbon Isotopes; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D020567:Fetal Weight; D005865:Gestational Age; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D018698:Glutamic Acid / Q000008:administration & dosage / Q000378:metabolism*; D005973:Glutamine / Q000008:administration & dosage / Q000378:metabolism*; D007262:Infusions, Intravenous; D019344:Lactic Acid / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000196:embryology* / Q000378:metabolism; D008102:Liver Circulation; D009929:Organ Size; D012756:Sheep; D014471:Umbilical Veins / Q000502:physiology
D001786:Blood Glucose; D002247:Carbon Isotopes; D005938:Glucocorticoids; D005973:Glutamine; D019344:Lactic Acid; D018698:Glutamic Acid; D003907:Dexamethasone; D005947:Glucose; D000409:Alanine