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The effect of hyperglycaemia on sugar transport was studied by comparing transepithelial permeation and tissue content of 3-O-methyl-D-glucose (3-O-MG), beta-methyl-D-glucoside (beta-MDG) and D-glucose in isolated mucosae of guinea-pig jejunum mounted in a flux chamber. Sugars were administered either to the luminal or the blood side of mucosae prepared either from normal animals or those maintained in a hyperglycaemic state by I.V. glucose infusion for 12 h. In control animals, absorptive sugar fluxes increased in the order glucose greater than beta-MDG greater than 3-O-MG. Only beta-MDG was accumulated in the tissue beyond the medium concentration. Permeation of 3-O-MG and beta-MDG in the direction blood-to-lumen was mainly paracellular as indicated by the strict correlation with the simultaneous permeation of polyethylene glycol (mol. wt. 900). Luminal addition of 10(-3) M-phlorhizin increased permeation and decreased tissue content of beta-MDG and D-glucose when administered on the blood side, suggesting that these sugars are recaptured at the brush border even from vigorously mixed solutions. For flux coefficient calculation the preparation was regarded as a three-compartment system. With all three sugars, the influx coefficient was higher at the luminal, but lower at the basolateral membrane than the corresponding efflux coefficient. 3-O-MG displayed the highest basolateral influx coefficient of all three sugars, being even higher than its luminal influx coefficient. The luminal influx coefficient of beta-MDG was 22 times greater, and its basolateral efflux coefficient 2.5 times less than the corresponding values for 3-O-MG, resulting in cellular beta-MDG accumulation. D-Glucose was suited best for transepithelial transport, having a luminal influx coefficient only 1.6 times less, and a basolateral efflux coefficient almost 10 times greater than those for beta-MDG. Prolonged hyperglycaemia increased the lumen-to-blood permeation of all three sugars 1.3-2-fold. No significant differences in tissue content to control values were observed after 45 min (3-O-MG, D-glucose) or 90 min (beta-MDG) incubation. Therefore, flux coefficients increased by the same factors in luminal and basolateral membranes, i.e. 1.7, 1.3 and 1.7 for 3-O-MG, beta-MDG and D-glucose, respectively. These results indicate that changes in both the luminal and basolateral membranes play a role in the increase of sugar transport in hyperglycaemia and that a regulatory mechanism might exist between the transport systems located in both membranes.(ABSTRACT TRUNCATED AT 400 WORDS)