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Molecular Nutrition
Abbreviations: BBMV, brush-border membrane vesicle; CHO, carbohydrate; SGLT1, Na+/glucose co-transporter 1; PVDF, polyvinylidene fluoride; Tris, 2-amino-2-hydroxymethyl-propane-1,3-diol
The classical model of intestinal sugar transport is that glucose and galactose are transported from the lumen of the intestine into enterocytes by the Na+/glucose co-transporter 1 (SGLT1), whereas fructose is transported by a facilitated, Na-independent transporter, GLUT5. Glucose, galactose and fructose, once accumulated in the cells, are released from the cytosol across the basolateral membrane into the systemic system by another facilitated Na+-independent monosaccharide transporter, GLUT2(1,2).
It has been suggested, however, that in the intestine of rodents, in response to a high-carbohydrate (CHO) diet, or intestinal infusion with high concentrations of glucose or fructose, GLUT2 is translocated to the luminal membrane of enterocytes to absorb dietary glucose or fructose(3,4), implying that GLUT2, as well as SGLT1, is involved in the uptake of dietary sugars. In support of this proposition Gouyon et al.(5) have reported that in GLUT2-knockout mice, fructose uptake in the intestinal brush-border membrane vesicles (BBMV) was half of that in the wild-type mice, indicating that brush-border membrane GLUT2 absorbs 50 % of luminal fructose(5).
In contrast, it has been demonstrated by Barone et al.(6) that GLUT5-knockout mice cannot absorb fructose. Furthermore, these workers have shown that the absorption of glucose across the brush-border membrane of GLUT5-knockouts is solely accomplished by SGLT1, concluding the lack of involvement of luminal GLUT2 in monosaccharide absorption(6). Moreover, in glucose-galactose malabsorption, which results from mutations within the SGLT1 gene(7,8), human infants cannot absorb glucose or galactose. Fructose, however, can be absorbed normally(7), indicating the presence of a functional transcellular route via luminal GLUT5 and basolateral GLUT2 for the absorption of fructose. The presence of GLUT2 on the luminal membrane would forestall the chronic and potentially fatal diarrhoea experienced by these children, suggesting that the expression of GLUT2 on the luminal membrane does not extend to humans.
In the light of these controversies it was essential to identify the candidate glucose transporter...