L-Glutamine

American Journal of physiology. Gastrointestinal and Liver Physiology, 01 Sep 2004, 287(3):G510-7。

L-Glutamine ameliorates acetaldehyde-induced increase in paracellular permeability in Caco-2 cell monolayer.[Reference: WebLink]

METHODS AND RESULTS:
Role of L-Glutamine in the protection of intestinal epithelium from acetaldehyde-induced disruption of barrier function was evaluated in Caco-2 cell monolayer. L-Glutamine reduced the acetaldehyde-induced decrease in transepithelilal electrical resistance and increase in permeability to inulin and lipopolysaccharide in a time- and dose-dependent manner; d-glutamine, L-aspargine, L-arginine, L-lysine, or L-alanine produced no significant protection. The glutaminase inhibitor 6-diazo-5-oxo-L-norleucine failed to affect the L-Glutamine-mediated protection of barrier function. L-Glutamine reduced the acetaldehyde-induced redistribution of occludin, zonula occludens-1 (ZO-1), E-cadherin, and beta-catenin from the intercellular junctions. Acetaldehyde dissociates occludin, ZO-1, E-cadherin, and beta-catenin from the actin cytoskeleton, and this effect was reduced by L-Glutamine. L-Glutamine induced a rapid increase in the tyrosine phosphorylation of EGF receptor, and the protective effect of L-Glutamine was prevented by AG1478, the EGF-receptor tyrosine kinase inhibitor.
CONCLUSIONS:
These results indicate that L-Glutamine prevents acetaldehyde-induced disruption of the tight junction and increase in the paracellular permeability in Caco-2 cell monolayer by an EGF receptor-dependent mechanism.

Diabetologia, 1981, 63(2):112-118.

The stimulus-secretion coupling of amino acid-induced insulin release. IV. Ionic response to L-Leucine and L-Glutamine.[Reference: WebLink]

METHODS AND RESULTS:
L-Glutamine enhances insulin release evoked by L-leucine in isolated rat pancreatic islets. The enhancing action of L-Glutamine, which is a rapid but steadily increasing and not rapidly reversible phenomenon is not attributable to any major change in either K+ or Ca2+ outflow from the islet cells. It coincides with an apparent increase in Ca2+ inflow rate and, hence, with Ca accumulation in the islets. The initial ionic response to L-leucine is not qualitatively altered by the presence of L-Glutamine. In their combined capacity to stimulate 45Ca net uptake in the islets, L-Glutamine can be replaced by L-asparagine but not by L-glutamate, whereas L-leucine can be replaced by L-norvaline or L-isoleucine, but not by L-valine, glycine or L-lysine. Such a specificity is identical to that characterizing the effect of these various amino acids upon insulin release.
CONCLUSIONS:
It is postulated that the release of insulin evoked by the combination of L-leucine and L-Glutamine involves essentially the same remodelling of ionic fluxes as that evoked by other nutrient secretagogues with, however, an unusual time course for the functional response to L-Glutamine.

Amino Acids, 2009, 37(1):131-142.

L-Glutamine or L-alanyl-L-glutamine prevents oxidant- or endotoxin-induced death of neonatal enterocytes.[Reference: WebLink]

This study tested the hypothesis that L-Glutamine (Gln) or L-alanyl-L-Glutamine (Ala-Gln) prevents oxidant- or endotoxin-induced death of neonatal enterocytes. Enterocytes of neonatal pigs rapidly hydrolyzed Ala-Gln and utilized Gln.
METHODS AND RESULTS:
To determine whether Gln or Ala-Gln has a cytoprotective effect, IPEC-1 cells were cultured for 24 h in Gln-free Dulbecco’s modified Eagle’s-F12 Ham medium containing 0, 0.5, 2.0 or 5.0 mM Gln or Ala-Gln, and 0, 0.5 mM H2O2 or 30 ng/ml lipopolysaccharide (LPS). Without Gln or Ala-Gln, H2O2- or LPS-treated cells exhibited almost complete death. Gln or Ala-Gln at 0.5, 2 and 5 mM dose-dependently reduced H2O2- or LPS-induced cell death by 14, 54 and 95%, respectively, whereas D-glutamine, alanine, glutamate, ornithine, proline, glucosamine or nucleosides had no effect. To evaluate the effectiveness of Gln or Ala-Gln in vivo, 7-day-old piglets received one-week oral administration of Gln or Ala-Gln (3.42 mmol/kg body weight) twice daily and then a single intraperitoneal injection of LPS (0.1 mg/kg body weight); piglets were euthanized in 24 and 48 h to analyze intestinal apoptotic proteins and morphology. Administration of Gln or Ala-Gln to LPS-challenged piglets increased Gln concentrations in small-intestinal lumen and plasma, reduced intestinal expression of Toll-like receptor-4, active caspase-3 and NFkB, ameliorated intestinal injury, decreased rectal temperature, and enhanced growth performance. These results demonstrate a protective effect of Gln or Ala-Gln against H2O2- or LPS-induced enterocyte death.
CONCLUSIONS:
The findings support addition of Gln or Ala-Gln to current Gln-free pediatric amino acid solutions to prevent intestinal oxidative injury and inflammatory disease in neonates.