Acute enterocyte adaptation to luminal glucose: a posttranslational mechanism for rapid apical recruitment of the transporter GLUT2

Abstract

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 μmol from 2.1 ± 0.1 μmol, 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.

Figure 1

In vivo Carrier-mediated glucose absorption at 10 and 100 mM glucose

Figure 2

a) Inhibition of in vivo glucose absorption by phloretin (PT) and phlorizin (PZ) at 10 mM glucose (black arrow at 60 min represents administration of inhibitor). b) Figure 2B Inhibition of in vivo glucose absorption by phloretin (PT) and phlorizin (PZ) at 100 mM glucose (black arrow at 60 min represents administration of inhibitor).

Figure 2

a) Inhibition of in vivo glucose absorption by phloretin (PT) and phlorizin (PZ) at 10 mM glucose (black arrow at 60 min represents administration of inhibitor). b) Figure 2B Inhibition of in vivo glucose absorption by phloretin (PT) and phlorizin (PZ) at 100 mM glucose (black arrow at 60 min represents administration of inhibitor).

Figure 3

Western blot of brush border membrane of mucosal scraping. a) Western blot of GLUT2 and the housekeeper gene GAPDH; b) semiquantitative ratio of GLUT2 to GAPDH in brush border membrane fraction.