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Differential Ileal Adaptation After Massive Proximal-Based Small Bowel Resection: Importance of the GLUT2 Hexose Transporter
Michael G. Sarr, Corey W. Iqbal*, Javairiah Fatima, Molly E. Gross
Department of Surgery, Mayo Clinic, Rochester, MN
Introduction: SGLT1 and GLUT2 are the predominant glucose transporters in rat intestine but are present in low quantities in the ileum where very little glucose absorption occurs normally; however, glucose uptake in the ileum is highly adaptable after small bowel resection.
Hypothesis: Ileal adaptability for glucose absorption after jejunal resection is mediated predominately by an increase in GLUT2.
Methods: Lewis rats (250-300 g) underwent massive (70%) proximal-based jejunoileal resection (starting at the duodenojejunal junction). Transporter-mediated glucose uptake was measured in the proximal and distal aspects of the remnant ileum at 1 and 4 wk postoperatively (n=6 each) in 20 mM D-glucose using the everted sleeve technique. Corresponding segments of ileum in naïve control and 1-wk sham laparotomy rats (n=6 each) were also studied. Selective inhibitors of hexose transporters were then evaluated. Phlorizin (0.2 M) was used to inhibit SGLT1-mediated glucose uptake and indirectly any uptake by GLUT2 by inhibiting GLUT2 trafficking to the apical membrane (Iqbal et al, Gastroenterology 2007; 132(4): A-891); phloretin (1 M) was used to inhibit GLUT2-mediated glucose uptake. Villous height of the proximal ileum was measured to assess for ileal adaptation.
Results: There was essentially no transporter-mediated glucose uptake in control or sham rat ileum. After massive 70% proximal intestinal resection, the proximal aspect of the remnant ileum had markedly greater glucose uptake at 4wk compared to controls and shams (80 vs 0 nmol/cm/min, p<0.0001). In the terminal ileum, there was little increase in uptake (9 vs 0 nmol/cm/min, p=0.17). Treatment with phlorizin (SGLT1 inhibition and indirect GLUT2 inhibition) led to complete inhibition of transporter-mediated glucose uptake in resected rats in both proximal and terminal ileum. Phloretin (GLUT2 inhibition) also inhibited completely transporter-mediated glucose uptake 4 wk after resection in both proximal (0 vs 80 nmol/cm/min, p<0.0001) and terminal ileum (0 vs 9 nmol/cm/min, p=0.17); there was partial inhibition in the proximal ileum for the 1-wk resection group (1.4 vs 11 nmol/cm/min, p=0.05). Histology of proximal ileum at 4 wk demonstrated markedly greater villous height compared to controls (500 vs 200 µm, p=0.0001).
Conclusions: Terminal ileum is not as adaptable as proximal ileum after proximal small intestinal resection. Complete inhibition of glucose uptake at 4 wk with either phlorizin or phloretin suggests that GLUT2 is the primary glucose transporter in the adapted ileum. (Support: NIH DK39337 [MGS]).
