Corticosteroids reverse the inhibition of Na-glucose cotransport in the chronically inflamed rabbit ileum.

In a rabbit model of chronic ileal inflammation, we previously demonstrated inhibition of Na-glucose cotransport (SGLT-1). The mechanism of 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. In this study, we determined the effect of methylprednisolone (MP) on SGLT-1 inhibition during chronic ileitis. Treatment with MP almost completely reversed the reduction in SGLT-1 in villus cells from the chronically inflamed ileum. MP also reversed the decrease in Na-K-ATPase activity in villus cells during chronic ileitis. However, MP treatment reversed the SGLT-1 inhibition in villus cell brush-border membrane vesicles from the inflamed ileum, which suggested an effect of MP at the level of the cotransporter itself. Kinetic studies demonstrated that the reversal of SGLT-1 inhibition by MP was secondary to an increase in the maximal velocity for glucose without a change in the affinity. Analysis of immunoreactive protein levels of the cotransporter demonstrated a restoration of the cotransporter numbers after MP treatment in the chronically inflamed ileum. Thus MP treatment alleviates SGLT-1 inhibition in the chronically inflamed ileum by increasing the number of cotransporters and not solely secondary to enhancing the activity of Na-K-ATPase or by altering the affinity for glucose.