The diffusive component of intestinal glucose absorption is mediated by the glucose-induced recruitment of GLUT2 to the brush-border membrane.
We have investigated the mechanism responsible for the diffusive component of intestinal glucose absorption, the major route by which glucose is absorbed. In perfused rat jejunum in vivo, absorption was strongly inhibited by phloretin, an inhibitor of GLUT2. The GLUT2 level at the brush-border membrane increased some 2-fold when the luminal glucose concentration was changed from 0 to 100 mM. The phloretin-sensitive or diffusive component of absorption appeared superficially linear and consistent with simple diffusion, but was in fact carrier-mediated and co-operative (n=1.6, [G(1/2)]=56 mM; where [G(1/2)] is the glucose concentration at half V(max)) because of the glucose-induced activation and recruitment of GLUT2 to the brush-border membrane. Diffusive transport by paracellular flow was negligible. The phloretin-insensitive, SGLT1-mediated, component of glucose absorption showed simple saturation kinetics with [G(1/2)]=27 mM: the activation of protein kinase C (PKC) betaII, the isoenzyme of PKC that most probably controls GLUT2 trafficking [Helliwell, Richardson, Affleck and Kellett (2000) Biochem. J. 350, 149-154], also showed simple saturation kinetics, with [G(1/2)]=21 mM. We conclude that the principal route for glucose absorption is by GLUT2-mediated facilitated diffusion across the brush-border membrane, which is up to 3-fold greater than that by SGLT1; the magnitude of the diffusive component at any given glucose concentration correlates with the SGLT1-dependent activation of PKC betaII. The implications of these findings for the assimilation of sugars immediately after a meal are discussed.
Kellett
G L
GL
Department of Biology, University of York, PO Box 373, York YO10 5YW, U.K. glk1@york.ac.uk
Helliwell
P A
PA
D000818:Animals; D001692:Biological Transport; D002851:Chromatography, High Pressure Liquid; D004058:Diffusion; D051273:Glucose Transporter Type 2; D007408:Intestinal Absorption / Q000187:drug effects; D007583:Jejunum / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008871:Microvilli / Q000201:enzymology / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D010693:Phloretin / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D051269:Sodium-Glucose Transporter 1
D051273:Glucose Transporter Type 2; D008562:Membrane Glycoproteins; D009004:Monosaccharide Transport Proteins; C495676:Slc5a1 protein, rat; D051269:Sodium-Glucose Transporter 1; D011493:Protein Kinase C; D010693:Phloretin