Intestinal D-galactose transport in an endotoxemia model in the rabbit.
Lipopolysaccharide (LPS) is an endotoxin causing sepsis. Studies from our laboratory revealed impaired intestinal absorption of L-leucine and D-fructose in LPS-treated rabbits. The aim of this study was to examine intestinal D-galactose transport following intravenous administration of LPS in the rabbit and to identify the cellular mechanisms driving this process. Endotoxin treatment diminished the buildup of D-galactose in intestinal tissue, the mucosal to serosal transepithelial flux of the sugar and its uptake by brush border membrane vesicles (BBMVs). Intracellular signaling pathways associated with protein kinase C (PKC), protein kinase A (PKA), p38 mitogen-activated protein kinase (p38MAPK), Jun N-terminal kinase (JNK), MAPK/extracellular signal-regulated kinases 1 and 2 (MEK1/2) and proteasome were found to be involved in this reduction in sugar uptake. Na(+)/glucose cotransporter 1 (SGLT1) protein levels in BBMVs were lower for LPS-treated animals than control animals. These findings indicate that LPS inhibits the intestinal absorption of D-galactose via a complex cellular mechanism that could involve posttranscriptional regulation of the SGLT1 transporter.
Amador
P
P
Physiology Unit, Department of Pharmacology and Physiology, Veterinary Faculty, University of Zaragoza, Miguel Servet 177, E-50013 Zaragoza, Spain.
García-Herrera
J
J
Marca
M C
MC
de la Osada
J
J
Acín
S
S
Navarro
M A
MA
Salvador
M T
MT
Lostao
M P
MP
Rodríguez-Yoldi
M J
MJ
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D015152:Blotting, Northern; D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D019446:Endotoxemia / Q000139:chemically induced / Q000378:metabolism*; D005690:Galactose / Q000378:metabolism* / Q000493:pharmacokinetics; D007093:Imidazoles / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D011817:Rabbits; D051269:Sodium-Glucose Transporter 1 / Q000235:genetics / Q000378:metabolism
D002070:Butadienes; D007093:Imidazoles; D008070:Lipopolysaccharides; D009570:Nitriles; D011725:Pyridines; D051269:Sodium-Glucose Transporter 1; C113580:U 0126; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; C093642:SB 203580; D005690:Galactose