Further studies of proximal tubular brush border membraned-glucose transport heterogeneity

Abstract

The properties of two sodium-dependent D-glucose transporters previously identified in renal proximal tubule brush border membrane (BBM) vesicles are studied. The low-affinity system, found in BBM vesicles from the outer cortex (early proximal tubule), is shown to be associated with the high-affinity phlorizin binding site typically found in renal BBM preparations. The high-affinity system, found in BBM vesicles from the outer medulla (late proximal tubule), is almost two orders of magnitude less sensitive to inhibition by phlorizin and is apparently not associated with high-affinity phlorizin binding. The sodium/glucose stoichiometry of the outer medullary transporter is found to be 2:1 by two independent methods. Previous measurements have established that the stoichiometry of the outer cortical system is 1:1. It is suggested that this arrangement of transporters in series along the proximal tubule enables the kidney to reabsorb glucose from the urine in an energy-efficient fashion. The bulk of the glucose load is reabsorbed early in the proximal tubule at an energetic cost of one Na+ per glucose molecule. Then in the late proximal tubule a larger coupling ratio and hence a larger driving force is employed to reabsorb the last traces of glucose from the urine.

The human kidney low affinity Na+/glucose cotransporter SGLT2. Delineation of the major renal reabsorptive mechanism for D-glucose.

“…The 1-min ['4C] aMeGlc uptake was within the linear range ofuptake and was 19±0.8 pmol/oocyte per min (n = 8). The Na+ to glucose coupling ratio for SGLT1 is therefore 2:1, consistent with the studies of SGLT1 expressed in oocytes ( 14) and with the known stoichiometry of the high affinity Na+/ glucose cotransport in brush border membrane vesicles ( 12,30,31).…”

“…A ratio of 1 Na' to 1 glucose is also consistent with the stoichiometric analysis of low affinity Na+/glucose cotransport in renal outer cortex brush border membrane vesicles ( 12,29).…”

“…We conclude, therefore, that kidney-specific low affinity SGLT2 is expressed in SI proximal tubule segments where the majority of filtered glucose is absorbed. All properties of SGLT2 determined so far are consistent with those of the kidney-specific low affinity/high capacity Na+-glucose cotransport system, which has been characterized in the past by studies using perfused tubule segments and using brush border membrane vesicles (5,8,11,12,29).…”

“…Other work indicated that r-galactose is a good substrate for the high affinity but not for the low affinity Na+/glucose cotransporter ( 11). Glucose uptake studies into brush border membrane vesicles from rabbit and human kidney cortex are in agreement with the existence oftwo renal Na+/glucose cotransporters (11)(12)(13)(14). The studies provided evidence for a low affinity transporter with a Km of 6 mM and a high affinity transporter with a Km of -0.3 mM and demonstrated a Na+ to glucose stoichiometry of 1:1 for the low affinity Na+/glucose cotransporter and of 2:1 for the high affinity Na+/glucose cotransporter.…”

Transepitheliald-glucose andd-fructose transport across the American lobster,Homarus americanus, intestine

“…Furthermore, the sodium coupling coefficient with transported D-glucose varied from 1:1 in the pyloric caeca to 2:1 for the upper intestine, providing for an efficient and complete sugar withdrawal process as the sugar moved along the substrate gradient. A similar linear heterogeneous arrangement of sodium-dependent D-glucose transporters has been reported for mammalian proximal tubule where a lower affinity SGLT2, displaying a 1:1 sodium co-transport stoichiometry, occurs immediately after the glomerulus, and is followed by a high affinity SGLT1 transporter with a 2:1 co-transport stoichiometry, together effectively removing all of the filtered D-glucose from the proximal tubule prior to the loop of Henle (Turner and Moran, 1982a;Turner and Moran, 1982b).…”