title: Intestinal fructose transport and malabsorption in humans.
abstract: Fructose is a hexose sugar that is being increasingly consumed in its monosaccharide form. Patients who exhibit fructose malabsorption can present with gastrointestinal symptoms that include chronic diarrhea and abdominal pain. However, with no clearly established gastrointestinal mechanism for fructose malabsorption, patient analysis by the proxy of a breath hydrogen test (BHT) is controversial. The major transporter for fructose in intestinal epithelial cells is thought to be the facilitative transporter GLUT5. Consistent with a facilitative transport system, we show here by analysis of past studies on healthy adults that there is a significant relationship between fructose malabsorption and fructose dose (r = 0.86, P < 0.001). Thus there is a dose-dependent and limited absorption capacity even in healthy individuals. Changes in fructose malabsorption with age have been observed in human infants, and this may parallel the developmental regulation of GLUT5 expression. Moreover, a GLUT5 knockout mouse has displayed the hallmarks associated with profound fructose malabsorption. Fructose malabsorption appears to be partially modulated by the amount of glucose ingested. Although solvent drag and passive diffusion have been proposed to explain the effect of glucose on fructose malabsorption, this could possibly be a result of the facilitative transporter GLUT2. GLUT5 and GLUT2 mRNA have been shown to be rapidly upregulated by the presence of fructose and GLUT2 mRNA is also upregulated by glucose, but in humans the distribution and role of GLUT2 in the brush border membrane are yet to be definitively decided. Understanding the relative roles of these transporters in humans will be crucial for establishing a mechanistic basis for fructose malabsorption in gastrointestinal patients.
authors.affiliation: Mechanisms in Cell Biology and Disease Research Group, Sansom Institute for Health Research, Univ. of South Australia, South Australia 5001, Australia.
authors.forename: Hilary F
authors.initials: HF
authors.lastname: Jones
authors.forename: Ross N
authors.initials: RN
authors.lastname: Butler
authors.forename: Doug A
authors.initials: DA
authors.lastname: Brooks
mesh_terms: D000042:Absorption; D000375:Aging / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D001944:Breath Tests; D045853:Exhalation; D005632:Fructose / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D051273:Glucose Transporter Type 2 / Q000378:metabolism; D051296:Glucose Transporter Type 5 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006859:Hydrogen; D007413:Intestinal Mucosa / Q000378:metabolism*; D008286:Malabsorption Syndromes / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D009154:Mutation
chemical_list: D051273:Glucose Transporter Type 2; D051296:Glucose Transporter Type 5; D005632:Fructose; D006859:Hydrogen; D005947:Glucose