Mechanism of inhibition of Na+-glucose cotransport in the chronically inflamed rabbit ileum

In a rabbit model of chronic ileal inflammation, we previously demonstrated that coupled NaCl absorption was reduced because of an inhibition of Cl-/HCO3- but not Na+/H+ exchange on the brush-border membrane (BBM) of villus cells. In this study we determined the alterations in Na+-stimulated glucose [Na+-O-methyl-D-glucose (Na+-OMG)] absorption during chronic ileitis. Na+-OMG uptake was reduced in villus cells from the chronically inflamed ileum. Na+-K+-adenosinetriphosphatase (ATPase), which provides the favorable Naf gradient for this cotransporter in intact cells, was found to be reduced also. However, in villus cell BBM vesicles from the inflamed ileum Na+-OMG uptake was reduced as well, suggesting an effect at the level of the cotransporter itself. Kinetic studies demonstrated that Na+-OMG uptake in the inflamed ileum was inhibited by a decrease in the maximal rate of uptake for OMG without a change in the affinity. Analysis of steady-state mRNb and immunoreactive protein levels of this cotransporter demonstrates reduced expression. Thus Na+-glucose cotransport was inhibited in the chronically inflamed ileum, and the inhibition was secondary to a decrease in the number of cotransporters and not solely secondary to an inhibition of Na+-K+-ATPase or altered affinity for glucose.