BASOLATERAL D-GLUCOSE TRANSPORT ACTIVITY ALONG THE CRYPT-VILLUS AXIS IN RAT JEJUNUM AND UP-REGULATION INDUCED BY GASTRIC-INHIBITORY PEPTIDEAND GLUCAGON-LIKE PEPTIDE-2

Phloridzin-insensitive D-glucose uptake into enterocytes isolated sequ entially from along the crypt-villus axis showed the majority of trans port activity to reside in cells from the upper third of the villus. I n contrast, total postnuclear glucose transporter 2 (GLUT2) protein co ntent of the cells was high even close to the crypt and was almost con stant for the upper 80 % of the villi. A 4 h lumenal perfusion in vivo with 100 mM D-glucose prior to harvesting the enterocytes produced a 2-to 3-fold increase in phloridzin-insensitive D-glucose uptake which extended down 70% of the villus. Vascular infusion in vivo with either 800 pM gastric inhibitory polypeptide (GTP) or glucagon-like peptide- 2 (GLP-2) prior to harvesting enterocytes produced the same response a s lumenal glucose, while glucagon like peptide-1 (GLP-1) had no effect . Inclusion of 30 mu M brefeldin A (BFA), an inhibitor of protein traf ficking, in the lumenal perfusate produced a small, but not significan t, increase in the control uptake profile along the villus in isolated enterocytes. However, BFA significantly reduced the upregulation indu ced by lumenal glucose and vascular GIP and blocked the stimulation pr oduced by vascular GLP-2 Biotinylation of surface proteins and isolati on with protein A indicated that there was no change in the membrane a bundance of GLUT2 after GLP-2 treatment. These results are discussed i n relation to the role of gastrointestinal peptide hormones in control ling intestinal hexose transport and the possibility of protein traffi cking being involved in mediating the upregulation of GLUT2 activity i n the enterocyte basolateral membrane.