Abstract
Activation of intestinal Na+–glucose cotransport increases paracellular movement of inert tracers in cultured monolayers, isolated rodent intestinal mucosae, and in rodents in vivo. However, not all studies have demonstrated comparable effects on human intestinal paracellular absorption. We sought to assess the effects of Na+–glucose cotransport on paracellular absorption in human beings using a simple noninvasive assay. Study subjects drank six 200-ml doses of test solution, composed of 0.8% w/v creatinine (sufficient to overwhelm endogenous creatinine) in 277 mM glucose or mannitol and urine was collected. Intestinal creatinine absorption is paracellular. Once absorbed, creatinine is cleared into the urine. Therefore, urinary creatinine recovery reflects intestinal paracellular creatinine absorption. Total urinary creatinine recovery was 55% ± 4% of creatinine ingested with glucose and 38% ± 9% of creatinine ingested with mannitol (p < 0.001). Thus, intestinal paracellular absorption of creatinine is increased by the presence of luminal glucose. Our results are consistent with in vivo human regulation of mucosal permeability by Na+–glucose cotransport.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
Hediger MA, Coady MJ, Ikeda TS, Wright EM: Expression cloning and cDNA sequencing of the Na+/glucose cotransporter. Nature 330:379–381, 1987
Turk E, Zabel B, Mundlos S, Dyer J, Wright EM: Glucose/galactose malabsorption caused by a defect in the Na+/glucose cotransporter. Nature 350:354–356, 1991
Madara JL, Pappenheimer JR: Structural basis for physiological regulation of paracellular pathways in intestinal epithelia. J Membr Biol 100:149–164, 1987
Pappenheimer JR: Physiological regulation of transepithelial impedance in the intestinal mucosa of rats and hamsters. J Membr Biol 100:137–148, 1987
Pappenheimer JR, Reiss KZ: Contribution of solvent drag through intercellular junctions to absorption of nutrients by the small intestine of the rat. J Membr Biol 100:123–136, 1987
Pappenheimer JR: On the coupling of membrane digestion with intestinal absorption of sugars and amino acids. Am J Physiol 265:G409–G417, 1993
Atisook K, Carlson S, Madara JL: Effects of phlorizin and sodium on glucose-elicited alterations of cell junctions in intestinal epithelia. Am J Physiol 258:C77–C85, 1990
Atisook K, Madara JL: An oligopeptide permeates intestinal tight junctions at glucose-elicited dilatations. Implications for oligopeptide absorption. Gastroenterology 100:719–724, 1991
Sadowski DC, Meddings JB: Luminal nutrients alter tightjunction permeability in the rat jejunum: An in vivo perfusion model. Can J Physiol Pharmacol 71:835–839, 1993
Madara JL: Sodium-glucose cotransport and epithelial permeability. Gastroenterology 107:319–320, 1994
Turner JR, Madara JL: Physiological regulation of intestinal epithelial tight junctions as a consequence of Na+-coupled nutrient transport. Gastroenterology 109:1391–1396, 1995
Soergel KH: Showdown at the tight junction. Gastroenterology 105:1247–1250, 1993
Lane JS, Whang EE, Rigberg DA, Hines OJ, Kwan D, Zinner MJ, McFadden DW, Diamond J, Ashley SW: Paracellular glucose transport plays a minor role in the unanesthetized dog. Am J Physiol 276:G789–G794, 1999
Uhing MR, Kimura RE: Active transport of 3–O-methyl glucose by the small intestine in chronically catheterized rats. J Clin Invest 95:2799–2805, 1995
Fine KD, Santa Ana CA, Porter JL, Fordtran JS: Mechanism by which glucose stimulates the passive absorption of small solutes by the human jejunum in vivo. Gastroenterology 107:389–395, 1994
Fine KD, Santa Ana CA, Porter JL, Fordtran JS: Effect of D-glucose on intestinal permeability and its passive absorption in human small intestine in vivo. Gastroenterology 105:1117–1125, 1993
Schwartz RM, Furner JK, Levitt MD: Paracellular intestinal transport of six-carbon sugars is negligible in the rat. Gastroenterology 1995
Perez M, Barber A, Ponz F: In vivo increase of passive intestinal absorption by cotransporter activation in rat. Rev Esp Fisiol 49:259–264, 1993
Pappenheimer JR: Paracellular intestinal absorption of glucose, creatinine, and mannitol in normal animals: relation to body size. Am J Physiol 259:G290–G299, 1990
Turner JR, Rill BK, Carlson SL, Carnes D, Kerner R, Mrsny RJ, Madara JL: Physiological regulation of epithelial tight junctions is associated with myosin light-chain phosphorylation. Am J Physiol 273:C1378–C1385, 1997
Uhing MR, Kimura RE: The effect of surgical bowel manipulation and anesthesia on intestinal glucose absorption in rats. J Clin Invest 95:2790–2798, 1995
Madara JL: Tight junction dymnamics: Is paracellular transport regulated. Cell 53:497–498, 1992
Madara JL, Carlson S: Supraphysiologic L-tryptophan elicits cytoskeletal and macromolecular permeability alterations in hamster small intestinal epithelium in vitro. J Clin Invest 87:454–462, 1991
Pappenheimer JR, Volpp K: Transmucosal impedance of small intestine: correlation with transport of sugars and amino acids. Am J Physiol 263:C480–C493, 1992
Pappenheimer JR, Dahl CE, Karnovsky ML, Maggio JE: Intestinal absorption and excretion of octapeptides composed of D amino acids. Proc Natl Acad Sci USA 91:1942–1945, 1994
Ballard ST, Hunter JH, Taylor AE: Regulation of tightjunction permeability during nutrient absorption across the intestinal epithelium. Annu Rev Nutr 15:35–55, 1995
Madara JL: Regulation of the movement of solutes across tight junctions. Annu Rev Physiol 60:143–159, 1998
Jodal M, Fihn B-M, Sjøqvist A: Effect of glucose on passive transport of extracellular probes across the rat small intestinal epithelium in vivo. Gastroenterology 107:A241, 1994
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Turner, J.R., Cohen, D.E., Mrsny, R.J. et al. Noninvasive In vivo Analysis of Human Small Intestinal Paracellular Absorption: Regulation by Na+-Glucose Cotransport. Dig Dis Sci 45, 2122–2126 (2000). https://doi.org/10.1023/A:1026682900586
Issue Date:
DOI: https://doi.org/10.1023/A:1026682900586