Characteristics of glucose-phlorizin interactions in isolated proximal tubules

Characteristics of phlorizin's interaction with the bidirectional fluxes of glucose were examined using isolated proximal convoluted tubules from the rabbit kidney. Radioisotopic glucose fluxes were determined with artificial perfusates having glucose concentrations of 5-15 mM. Rabbit serum was used as the bath. Phlorizin in intraluminal concentrations of 10(-7) to 10(-4) M progressively reduced the lumen-to-bath flux of glucose without affecting the bath-to-lumen flux. At 10(-4) M phlorizin in the lumen, the lumen-to-bath flux decreased from 92.86 +/- 5.71 to 7.83 +/- 3.04 pmol/mm.min (P less than 0.001), with bath-to-lumen fluxes averaging 4.58 +/- 0.58 pmol/mm-min. Similar changes occurred when phlorizin was added to the bath, although concentrations approximately 10-100 times higher were required. Phlorizin 10(-3) M in the bath also reduced the bath-to-lumen glucose flux from 10.20 +/- 3.07 to 7.16 +/- 2.20 pmol/mm.min (P less than 0.05). Phlorizin transport was passive. The kinetics of phlorizin's inhibition of the lumen-to-bath glucose flux were determined by varying the glucose delivery rate over a range of phlorizin concentrations. Phlorizin reduced the maximal glucose transport rate and increased the delivery rate of glucose at which glucose absorption was half maximal. These data indicate that the interaction of phlorizin with proximal renal glucose transport involves elements of both competitive and noncompetitive inhibition.