The Effect of Massive Small Bowel Resection and Oral Epidermal Growth Factor Therapy on SGLT-1 Distribution in Rabbit Distal Remnant

Abstract

Small bowel resection decreases brush border membrane (BBM) glucose uptake kinetics. Oral epidermal growth factor (EGF) returns net glucose transport across intact tissue to control levels despite persistence of a defect in BBM glucose uptake. The purpose of this study was to examine the effects of resection and EGF treatment on sodium-dependent glucose cotransporter 1 (SGLT-1) expression in distal remnant tissue. New Zealand White rabbits (1 kg) underwent 70% small bowel resection (R). One group of resected animals (R-EGF) received oral EGF (40 μg/kg, days 3-8). Distal remnant tissue was harvested 10 d after surgery, and compared with controls (C). Mucosal SGLT-1 mRNA was measured by Northern blot, BBM SGLT-1 content by Western blot, and villus distribution of SGLT-1 protein and mRNA by immunofluorescence and in situ hybridization. Western blot indicated BBM from both resected and EGF-treated tissue had decreased SGLT-1 content (C, 0.55 ± 0.04; R, 0.35 ± 0.04; R-EGF, 0.35 ± 0.03 trace OD; n = 5; p < 0.05). Northern blot revealed no alterations in mucosal SGLT-1 mRNA content in any group. SGLT-1 protein and mRNA localization in control tissues was characterized by a gradual increase in stain intensity from the base of the villus to the villus tip. Resection altered SGLT-1 protein and mRNA expression along the villus axis with intensity being strongest in the mid-villus region and little expression at the tip of the villus. Oral EGF normalized SGLT-1 protein and mRNA expression to control patterns. Resection alters SGLT-1 protein and mRNA expression along the villus axis, despite no change in total mucosal SGLT-1 mRNA content. EGF normalized villus SGLT-1 protein and mRNA distribution, without altering overall BBM SGLT-1 content or mucosal mRNA levels.