Glutamine Deprivation Alters Intestinal Tight Junctions via a PI3-K/Akt Mediated Pathway in Caco-2 Cells

Glutamine (GIP) is important for intestinal barrier function and regulation of tight junction (TJ) proteins, but the intracellular mechanisms of action remain undefined. The purpose of this study was to test the hypothesis that Gin regulates intercellular junction integrity and TJ proteins through the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in Caco-2 cells. Deprivation of exogenous and endogenous glutamine decreased transepithelial electrical resistance (TER) (P < 0.01) and increased permeability (P < 0.01). Both wortmannin and ILY294002, PI3K inhibitors, prevented the TER decrease and the permeability increase induced by Gln deprivation (P < 0.001). Gin deprivation also caused decreased TJ protein claudin-1 (P < 0.001). Both wortmannin and LY294002 treatment prevented this effect (P < 0.001). Deprivation of Gin increased phosphor-Akt protein. Gin supplementation reversed this effect. Decreased TER and increased permeability associated with Gin deprivation were not observed in small interfering RNA for p85 transfected Cacc-2 cells, In conclusion, Gill regulates intercellular junction integrity and TJ proteins through the PI3-3-Kinase/Akt pathway, J. Nutr. 139 710-714, 2009.