Crypt/villus site of substrate-dependent regulation of mouse intestinal glucose transporters.

The intestinal epithelium is in a constant state of turnover, with cells differentiating at the crypts and then migrating toward the tips of the villi. Does substrate-dependent regulation of intestinal Na+/D-glucose cotransporters occur only in crypt cells, or can transport activity be subsequently reprogrammed in mature enterocytes? We used in situ, glucose-protectable specific phlorizin binding to determine site density of brush border glucose transporters in enterocytes fractionated along the crypt/villus axis of mice that were killed shortly after drastic changes in carbohydrate levels of their diets. Dietary carbohydrate-induced changes in site density of specific phlorizin binding initially appeared only in crypt cells before spreading, over the course of several days, to the villus tips. Thus, only crypt cells perceive the signal for glucose transporter regulation, and the observed time lag of diet-induced changes in intestinal glucose uptake is due mainly to cell migration times.