Acute Enterocyte Adaptation to Luminal Glucose: A Posttranslational Mechanism for Rapid Apical Recruitment of the Transporter GLUT2

Background Glucose absorption postprandially increases markedly to levels far greater than possible by the classic glucose transporter sodium-glucose cotransporter 1 (SGLT1). Hypothesis Luminal concentrations of glucose >50 mM lead to rapid, phenotypic, non-genomic adaptations by the enterocyte to recruit another transporter, glucose transporter 2 (GLUT2), to the apical membrane to increase glucose absorption. Methods Isolated segments of jejunum were perfused in vivo with glucose-containing solutions in anesthetized rats. Carrier-mediated glucose uptake was measured in 10 and 100 mM glucose solutions (n=6 rats each) with and without selective inhibitors of SGLT1 and GLUT2. Results The mean rate of carrier-mediated glucose uptake increased in rats perfused with 100 mM versus 10 mM glucose to 13.9 +/- 2.9 mu mol from 2.1 +/- 0.1 mu mol, respectively (p<0.0001). Using selective inhibitors, the relative contribution of GLUT2 to glucose absorption was 56% in the 100 mM concentration of glucose compared to the 10 mM concentration (27%; p<0.01). Passive absorption accounted for 6% of total glucose absorption at 100 mM glucose. Conclusion A small amount of GLUT2 is active at the lesser luminal concentrations of glucose, but when exposed to concentrations of 100 mM, the enterocyte presumably changes its phenotype by recruiting GLUT2 apically to markedly augment glucose absorption.