Regulation of MonosacchaRide tRanspoRt

An additional monosaccharide transport pathway stems from the interesting findings that GLUT2, the classic facilitative glucose transporter initially believed to be sequestered to the basolateral membrane, as well as a novel facilitative glucose-specific transporter GLUT7 (SLC2A7), can both be inserted into the brush border in response to high glucose loads in the lumen of the small intestine.11, 16,19 This model requires glucose to initially be transported by SGLT1, whose activity triggers protein kinase C (PKC) and mitogen-activating protein kinase (MAP-K), the end effect of which is the rapid insertion of GLUT2 into the brush border.16 The rapid insertion of facilitative glucose (GLUT2 and GLUT7) and fructose (GLUT2) transport proteins in the apical brush border would then provide a pair of high-volume facilitative hexose transporters capable of handling the microclimate of high monosaccharide concentrated by brush-border dissacharidases.16,19,20 Figure 8-1A-C illustrates the various carrier-mediated pathways which dietary monosaccharides can be transported across the absorptive enterocyte. Figure 8-2 illustrates the difference between specific carrier-mediated monosaccharide transport that occurs via absorptive enterocytes lining the upper villus region, as well as paracellular solvent drag between adjacent enterocytes. Patients diagnosed with the rare genetic disorder known as Fanconi-Bickel disease demonstrate a defect in GLUT2 function. Accordingly, these patients present no classic basolateral hexose transport pathway. However, despite this defect, these patients can be managed with correct dietary manipulation. To this end, this condition has been studied and data indicates an alternative hexose delivery pathway wherein luminal glucose is transported into the cytoplasm via SGLT1. Subsequently, glucose is phosphorylated and transferred into the endoplasmic reticulum whereupon membrane-trafficking delivers glucose-containing vesicles to the basolateral membrane and hence delivered into the basolateral space.20-23 The crucial step in intestinal hexose transport remains sodium-coupled glucose transport through SGLT1. Following transport across the brush-border membrane, numerous signaling pathways, microclimate changes, and metabolic enzymes can act to regulate the rate of glucose hexose transport as well as the transfer of the absorbed hexoses into the basolateral space.24-28