The textbook view of intestinal absorption is that glucose enters the absorptive cell solely by SGLT1 in the brush-border membrane (BBM); it then exits into the blood by GLUT2 in the basolateral membrane (BLM). Fructose enters by GLUT5 and exits by GLUT2, so that glucose and fructose share a common exit pathway.
However, there is substantial evidence in the early literature that the major component of glucose absorption in vivo is passive: at high concentrations of glucose similar to those likely to be present at the BBM immediately after a meal, the passive route is some two to five times greater than the active route mediated by SGLT1. The passive component is not seen in vitro and has therefore been attributed to paracellular flow through tight junctions.
We have now obtained evidence that the passive component is in fact facilitated, being mediated by the glucose-dependent activation and recruitment of GLUT2 to the BBM: rapid trafficking and also activation (within minutes) of GLUT2 at the BBM correlates with the activation of PKC βII, which in turn is regulated by transport of glucose through SGLT1 (Kellett, 2001). In addition, fructose is transported across the BBM not only by GLUT5, but also by GLUT2. The actions of sugars and endogenous hormones in vivo combine to maintain activation of PKC βII and a high level of GLUT2 at the BBM. Excision of intestine for in vitro perfusions therefore causes rapid loss of the majority of GLUT2 from the BBM, explaining why the passive component has been seen previously only in vivo.
The loss of GLUT2 on excision explains in part why, when GLUT2 was first discovered, it was detected only at the BLM in immunocytochemical studies. If, however, jejunum is first perfused under conditions which promote trafficking of GLUT2 to the BBM and then fixed in vivo, clear staining at both the BLM and BBM is seen. Moreover, staining is stronger in jejunum perfused with 50 mM glucose than with 50 mM mannitol, confirming that glucose induces GLUT2 trafficking to the BBM.
The mechanism we have proposed provides a means whereby absorptive capacity is precisely and very rapidly regulated to match dietary intake.