Intestinal D-galactose transport in an endotoxemia model in the rabbit

J Membr Biol. 2007 Feb;215(2-3):125-33. doi: 10.1007/s00232-007-9012-5. Epub 2007 Jun 12.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport / drug effects
  • Blotting, Northern
  • Blotting, Western
  • Butadienes / pharmacology
  • Endotoxemia / chemically induced
  • Endotoxemia / metabolism*
  • Galactose / metabolism*
  • Galactose / pharmacokinetics
  • Imidazoles / pharmacology
  • Intestinal Mucosa / metabolism*
  • Intestines / drug effects
  • Lipopolysaccharides / administration & dosage
  • Lipopolysaccharides / pharmacology
  • Male
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism
  • Nitriles / pharmacology
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism
  • Pyridines / pharmacology
  • Rabbits
  • Sodium-Glucose Transporter 1 / genetics
  • Sodium-Glucose Transporter 1 / metabolism

Substances

  • Butadienes
  • Imidazoles
  • Lipopolysaccharides
  • Nitriles
  • Pyridines
  • Sodium-Glucose Transporter 1
  • U 0126
  • Protein Kinase C
  • Mitogen-Activated Protein Kinases
  • SB 203580
  • Galactose