RT Journal Article
T1 Metformin modifies glutamine metabolism in an in vitro and in vivo model of hepatic encephalopathy.
A1 Gil-GÓmez, Antonio
A1 Gómez-Sotelo, Ana Isabel
A1 Ranchal, Isidora
A1 Rojas, Ángela
A1 García-Valdecasas, Marta
A1 Muñoz-Hernández, Rocío
A1 Gallego-Durán, Rocío
A1 Ampuero, Javier
A1 Romero Gómez, Manuel
AB to analyze the effect of metformin on ammonia production derived from glutamine metabolism in vitro and in vivo. twenty male Wistar rats were studied for 28 days after a porto-caval anastomosis (n = 16) or a sham operation (n = 4). Porto-caval shunted animals were randomized into two groups (n = 8) and either received 30 mg/kg/day of metformin for two weeks or were control animals. Plasma ammonia concentration, Gls gene expression and K-type glutaminase activity were measured in the small intestine, muscle and kidney. Furthermore, Caco2 were grown in different culture media containing glucose/glutamine as the main carbon source and exposed to different concentrations of the drug. The expression of genes implicated in glutamine metabolism were analyzed. metformin was associated with a significant inhibition of glutaminase activity levels in the small intestine of porto-caval shunted rats (0.277 ± 0.07 IU/mg vs 0.142 ± 0.04 IU/mg) and a significant decrease in plasma ammonia (204.3 ± 24.4 µg/dl vs 129.6 ± 16.1 µg/dl). Glucose withdrawal induced the expression of the glutamine transporter SLC1A5 (2.54 ± 0.33 fold change; p  metformin regulates ammonia homeostasis by modulating glutamine metabolism in the enterocyte, exerting an indirect control of both the uptake and degradation of glutamine. This entails a reduction in the production of metabolites and energy through this pathway and indirectly causes a decrease in ammonia production that could be related to a decreased risk of HE development.
SN 1130-0108
YR 2018
FD 2018
LK http://hdl.handle.net/10668/12241
UL http://hdl.handle.net/10668/12241
LA en
DS RISalud
RD Apr 4, 2025