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. 2000 Aug 15;350(Pt 1):155–162.

The diffusive component of intestinal glucose absorption is mediated by the glucose-induced recruitment of GLUT2 to the brush-border membrane.

G L Kellett 1, P A Helliwell 1
PMCID: PMC1221237  PMID: 10926839

Abstract

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.

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Selected References

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  1. Cheeseman C. I. GLUT2 is the transporter for fructose across the rat intestinal basolateral membrane. Gastroenterology. 1993 Oct;105(4):1050–1056. doi: 10.1016/0016-5085(93)90948-c. [DOI] [PubMed] [Google Scholar]
  2. Cheeseman C. I. Upregulation of SGLT-1 transport activity in rat jejunum induced by GLP-2 infusion in vivo. Am J Physiol. 1997 Dec;273(6 Pt 2):R1965–R1971. doi: 10.1152/ajpregu.1997.273.6.R1965. [DOI] [PubMed] [Google Scholar]
  3. Corpe C. P., Basaleh M. M., Affleck J., Gould G., Jess T. J., Kellett G. L. The regulation of GLUT5 and GLUT2 activity in the adaptation of intestinal brush-border fructose transport in diabetes. Pflugers Arch. 1996 Jun;432(2):192–201. doi: 10.1007/s004240050124. [DOI] [PubMed] [Google Scholar]
  4. Crane R. K. The gradient hypothesis and other models of carrier-mediated active transport. Rev Physiol Biochem Pharmacol. 1977;78:99–159. doi: 10.1007/BFb0027722. [DOI] [PubMed] [Google Scholar]
  5. Debnam E. S., Levin R. J. An experimental method of identifying and quantifying the active transfer electrogenic component from the diffusive component during sugar absorption measured in vivo. J Physiol. 1975 Mar;246(1):181–196. doi: 10.1113/jphysiol.1975.sp010885. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ferraris R. P., Diamond J. Regulation of intestinal sugar transport. Physiol Rev. 1997 Jan;77(1):257–302. doi: 10.1152/physrev.1997.77.1.257. [DOI] [PubMed] [Google Scholar]
  7. Ferraris R. P., Yasharpour S., Lloyd K. C., Mirzayan R., Diamond J. M. Luminal glucose concentrations in the gut under normal conditions. Am J Physiol. 1990 Nov;259(5 Pt 1):G822–G837. doi: 10.1152/ajpgi.1990.259.5.G822. [DOI] [PubMed] [Google Scholar]
  8. Fischbarg J., Kuang K. Y., Vera J. C., Arant S., Silverstein S. C., Loike J., Rosen O. M. Glucose transporters serve as water channels. Proc Natl Acad Sci U S A. 1990 Apr;87(8):3244–3247. doi: 10.1073/pnas.87.8.3244. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ganesan S., Calle R., Zawalich K., Smallwood J. I., Zawalich W. S., Rasmussen H. Glucose-induced translocation of protein kinase C in rat pancreatic islets. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9893–9897. doi: 10.1073/pnas.87.24.9893. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hediger M. A., Coady M. J., Ikeda T. S., Wright E. M. Expression cloning and cDNA sequencing of the Na+/glucose co-transporter. 1987 Nov 26-Dec 2Nature. 330(6146):379–381. doi: 10.1038/330379a0. [DOI] [PubMed] [Google Scholar]
  11. Helliwell P. A., Richardson M., Affleck J., Kellett G. L. Regulation of GLUT5, GLUT2 and intestinal brush-border fructose absorption by the extracellular signal-regulated kinase, p38 mitogen-activated kinase and phosphatidylinositol 3-kinase intracellular signalling pathways: implications for adaptation to diabetes. Biochem J. 2000 Aug 15;350(Pt 1):163–169. [PMC free article] [PubMed] [Google Scholar]
  12. Helliwell P. A., Richardson M., Affleck J., Kellett G. L. Stimulation of fructose transport across the intestinal brush-border membrane by PMA is mediated by GLUT2 and dynamically regulated by protein kinase C. Biochem J. 2000 Aug 15;350(Pt 1):149–154. [PMC free article] [PubMed] [Google Scholar]
  13. Hirsh A. J., Cheeseman C. I. Cholecystokinin decreases intestinal hexose absorption by a parallel reduction in SGLT1 abundance in the brush-border membrane. J Biol Chem. 1998 Jun 5;273(23):14545–14549. doi: 10.1074/jbc.273.23.14545. [DOI] [PubMed] [Google Scholar]
  14. Lane J. S., Whang E. E., Rigberg D. A., Hines O. J., Kwan D., Zinner M. J., McFadden D. W., Diamond J., Ashley S. W. Paracellular glucose transport plays a minor role in the unanesthetized dog. Am J Physiol. 1999 Mar;276(3 Pt 1):G789–G794. doi: 10.1152/ajpgi.1999.276.3.G789. [DOI] [PubMed] [Google Scholar]
  15. Loo D. D., Zeuthen T., Chandy G., Wright E. M. Cotransport of water by the Na+/glucose cotransporter. Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):13367–13370. doi: 10.1073/pnas.93.23.13367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lostao M. P., Berjón A., Barber A., Ponz F. On the multiplicity of glucose analogues transport systems in rat intestine. Rev Esp Fisiol. 1991 Dec;47(4):209–216. [PubMed] [Google Scholar]
  17. Madara J. L., Pappenheimer J. R. Structural basis for physiological regulation of paracellular pathways in intestinal epithelia. J Membr Biol. 1987;100(2):149–164. doi: 10.1007/BF02209147. [DOI] [PubMed] [Google Scholar]
  18. Maenz D. D., Cheeseman C. I. The Na+-independent D-glucose transporter in the enterocyte basolateral membrane: orientation and cytochalasin B binding characteristics. J Membr Biol. 1987;97(3):259–266. doi: 10.1007/BF01869228. [DOI] [PubMed] [Google Scholar]
  19. Pappenheimer J. R. On the coupling of membrane digestion with intestinal absorption of sugars and amino acids. Am J Physiol. 1993 Sep;265(3 Pt 1):G409–G417. doi: 10.1152/ajpgi.1993.265.3.G409. [DOI] [PubMed] [Google Scholar]
  20. Pappenheimer J. R., Reiss K. Z. Contribution of solvent drag through intercellular junctions to absorption of nutrients by the small intestine of the rat. J Membr Biol. 1987;100(2):123–136. doi: 10.1007/BF02209145. [DOI] [PubMed] [Google Scholar]
  21. Pappenheimer J. R. Scaling of dimensions of small intestines in non-ruminant eutherian mammals and its significance for absorptive mechanisms. Comp Biochem Physiol A Mol Integr Physiol. 1998 Sep;121(1):45–58. doi: 10.1016/s1095-6433(98)10100-9. [DOI] [PubMed] [Google Scholar]
  22. Saxon M. L., Zhao X., Black J. D. Activation of protein kinase C isozymes is associated with post-mitotic events in intestinal epithelial cells in situ. J Cell Biol. 1994 Aug;126(3):747–763. doi: 10.1083/jcb.126.3.747. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Schultz S. G., Curran P. F. Coupled transport of sodium and organic solutes. Physiol Rev. 1970 Oct;50(4):637–718. doi: 10.1152/physrev.1970.50.4.637. [DOI] [PubMed] [Google Scholar]
  24. Semenza G., Kessler M., Hosang M., Weber J., Schmidt U. Biochemistry of the Na+, D-glucose cotransporter of the small-intestinal brush-border membrane. The state of the art in 1984. Biochim Biophys Acta. 1984 Sep 3;779(3):343–379. doi: 10.1016/0304-4157(84)90016-9. [DOI] [PubMed] [Google Scholar]
  25. Stevens B. R., Kaunitz J. D., Wright E. M. Intestinal transport of amino acids and sugars: advances using membrane vesicles. Annu Rev Physiol. 1984;46:417–433. doi: 10.1146/annurev.ph.46.030184.002221. [DOI] [PubMed] [Google Scholar]
  26. Thorens B., Cheng Z. Q., Brown D., Lodish H. F. Liver glucose transporter: a basolateral protein in hepatocytes and intestine and kidney cells. Am J Physiol. 1990 Dec;259(6 Pt 1):C279–C285. doi: 10.1152/ajpcell.1990.259.2.C279. [DOI] [PubMed] [Google Scholar]
  27. Wright E. M., Loo D. D., Turk E., Hirayama B. A. Sodium cotransporters. Curr Opin Cell Biol. 1996 Aug;8(4):468–473. doi: 10.1016/s0955-0674(96)80022-6. [DOI] [PubMed] [Google Scholar]

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