Mechanisms of ileal adaptation for glucose absorption after proximal-based small bowel resection

Introduction: The hexose transmembrane transporters SGLT1 and GLUT2 are present in low quantities in ileum where little glucose absorption occurs normally; however, glucose uptake in ileum is highly adaptable after small bowel resection. Hypothesis: Ileal adaptability for glucose absorption after jejunal resection is mediated predominately by upregulation of GLUT2. Methods: Rats underwent 70% proximal-based jejunoileal resection. Transporter-mediated glucose uptake was measured in proximal and distal remnant ileum 1 and 4 wk postoperatively (n = 6 rats, each) and in corresponding ileal segments in control and 1 wk sham laparotomy rats (n = 6, each) without and with selective inhibitors of SGLT1 and GLUT2. In separate groups of rats (n = 6, each), protein (Western blots), mRNA (reverse transcriptase polymerase chain reaction [RT-PCR]), and villus height (histomorphology) were measured. Results: After 70% proximal intestinal resection, there was no dramatic change in protein or mRNA expression per cell of either SGLT1 or GLUT2, but median glucose uptake (nmol/cm/min) increased markedly from 52 (range 28-63) in controls to 118 (range 80-171) at 1 wk, and 203 (range 93-248) at 4 wk (p ≤ 0.04 each) correlating with change in villus height (p ≤ 0.03). Conclusions: Ileal adaptation for glucose transport occurs through cellular proliferation (hyperplasia) and not through cellular upregulation of glucose transporters.