Effects of glutamine isomers on human (Caco-2) intestinal epithelial proliferation, strain-responsiveness, and differentiation

Enteral feeding with small amounts to stimulate bowel mobility, and glutami ne supplementation, which provides nutrients selectively used by intestinal epithelial cells, might preserve the gut mucosa during fasting. We evaluat ed the effects of the interaction between mechanical strain and glutamine s upplementation in human Caco-2 intestinal epithelial cells, and pursued the finding of equivalent effects of L- and D-glutamine in Caco-2, HT-29, and primary malignant human colonocytes. Caco-2 cells were subjected to repetit ive strain in media containing 2 mmol/L of L-glutamine and media supplement ed with L- or D-glutamine. Proliferation was determined by automated cell c ounting. Differentiation and cellular production of L-glutamine were determ ined spectroscopically. Rhythmic deformation stimulated Caco-2 proliferatio n in a frequency-dependent manner. Maximal stimulation occurred at 10 cpm. consistent with in vivo frequencies of peristalsis and villous mobility. De formation at 10 cpm and L-glutamine supplementation from 2 to 5 mmol/L conc entrations independently stimulated Caco-2 proliferation; the combination f urther increased proliferation. D-Glutamine supplementation yielded similar results, although with lesser potency. Furthermore, both L- and D-glutamin e equivalently reduced Caco-2 dipeptidyl dipeptidase activity. The effects of each isoform were blocked by 1 to 3 mmol/L acivicin. a selective antagon ist of glutamine metabolism. Indeed Caco-2 and HT-29 cells and primary mali gnant colonocytes each metabolized D-glutamine to L-glutamine. Glutamine su pplementation in fasting patients might prove synergistic with stimulation of bowel motility by non-nutritive feeding, whereas tissue-specific variati ons in D-glutamine metabolism might facilitate selective nutripharmaceutica l targeting of the gut mucosa.