Fructose reabsorption by rat proximal tubules: role of Na+-linked cotransporters and the effect of dietary fructose

Fructose consumption has increased because of widespread use of high-fructose corn syrup by the food industry. Renal proximal tubules are thought to reabsorb fructose. However, fructose reabsorption (J(fructose)) by proximal tubules has not yet been directly demonstrated, nor the effects of dietary fructose on J(fructose). This segment expresses Na+- and glucose-linked transporters (SGLTs) 1, 2, 4, and 5 and glucose transporters (GLUTs) 2 and 5. SGLT4 and -5 transport fructose, but SGLT1 and -2 do not. Knocking out SGLT5 increases urinary fructose excretion. We hypothesize that J(fructose) in the S2 portion of the proximal tubule is mediated by luminal entry via SGLT4/5 and basolateral exit by GLUT2 and that it is enhanced by a fructose-enriched diet. We measured J(fructose) by proximal straight tubules from rats consuming either tap water (Controls) or 20% fructose (FRU). Basal J(fructose) in Controls was 14.1 +/- 1.5 pmol.mm(-1).min(-1). SGLT inhibition with phlorizin reduced J(fructose) to 4.9 +/- 1.4 pmol.mm(-1) (P < 0.008), whereas removal of Na+ diminished J(fructose) by 86 +/- 5% (P < 0.0001). A fructose-enriched diet increased J(fructose) from 12.8 +/- 2.5 to 19.3 +/- 0.5 pmol-mm(-1).min(-1), a 51% increase (P < 0.03). Using immunofluorescence, we detected luminal SGLT4 and SGLT5 and basolateral GLUT2; GLUTS was undetectable. The expression of apical transporters SGLT4 and SGLT5 was higher in FRU than in Controls [137 +/- 10% (P < 0.01) and 38 +/- 14% (P < 0.04). respectively]. GLUT2 was also elevated by 88 +/- 27% (P < 0.02) in FRU. We conclude that J(fructose) by proximal tubules occurs primarily via Na+- linked cotransport processes, and a fructose-enriched diet enhances reabsorption. Transport across luminal and basolateral membranes is likely mediated by SGLT4/5 and GLUT2, respectively.