Glutamine signaling in intestinal cells

Glutamine (Gln) is a "competence factor" necessary for intestinal cell prol iferation, intestinal fluid/ electrolyte absorption, and mitogenic response to growth factors. Gin deprivation produces apoptosis. GIn stimulation of quiescent cells produces immediate-early gene expression and MAP kinase act ivation. However, EGF signals more powerfully through MAPKs than Gln. Inter estingly, EGF-stimulated mitogenesis is ineffective in the absence of Gln. In the intact intestinal epithelia in vivo, Gin has powerful effects on abs orption of sodium and chloride. Gin-stimulated absorption is greater than a nd additive to glucose-stimulated absorption in cryptosporidial enteritis; In the piglet ileum, Gin metabolism stimulates apical amiloride-inhibitable Na+/H+ exchange. Although one might predict powerful effects of oral Gin o n absorption in babies with diarrhea, 3 clinical trials to date (one publis hed) have not shown an advantage of Gin-supplemented oral rehydration solut ions (ORS) compared to standard glucose ORS. Severely dehydrated subjects h ave not been studied. More important effects of Gin treatment may be seen w ith (1) ca-administration with a growth factor and (2) in patients with sev ere intestinal damage, such as protracted diarrhea of infancy or AIDS enter opathy.