Crypt-villus site of glucose transporter induction by dietary carbohydrate in mouse intestine.

Intestinal brush-border glucose uptake rate is regulated by dietary carbohydrate level. However, this uptake response takes a day or more after a change in dietary carbohydrate level. Is this dietary signal perceived in the crypts, and is the glucose transporter activity of enterocytes irreversibly programmed there? If so, this time lag could reflect cell migration times along the crypt-villus axis, since glucose transport is not fully expressed until cells reach the midvillus. Alternatively, however, the time lag could arise from the induction process itself, if glucose transporter activity in mature villus enterocytes can be reversibly reprogrammed by dietary carbohydrate levels. Hence, we measured glucose-protectable phlorizin binding (as a measure of glucose transporter site density) in mouse enterocytes fractionated along the crypt-villus axis by the Weiser method, as a function of time after an abrupt switch in dietary carbohydrate level. For an increase or decrease in dietary carbohydrate, an increase or decrease in phlorizin binding site density first appeared in the crypts and marched over the course of several days to the villus tips. Hence, the signal for glucose transporter regulation is perceived in the crypts, and the observed lag in uptake is due largely to cell migration times.