Mechanism of glycosuria during volume expansion superimposed on subthreshold glucose loading.

In order to elucidate the mechanism of glycosuria, clearance and micropuncture studies were performed in 19 dogs before and after subthreshold glucose loading and again after superimposition of extracellular volume expansion. Subthreshold glucose loading inhibited proximal sodium reabsorption and increased proximal glucose reabsorption, demonstrating dissociation between net sodium and glucose transport. Glucose delivery out of the proximal convoluted tubule was greatly increased by the combined effect of increased filtered load of glucose and reduced fractional proximal fluid reabsorption. There was a remarkable compensatory increase in glucose reabsorption in the segment between late proximal tubule and distal tubule (intermediate segment) and glycosuria did not occur. When 10% extracellular volume expansion was superimposed on the ongoing subthreshold glucose loading, absolute proximal glucose reabsorption was inhibited. This led to an additional increase in glucose delivery to the intermediate segment, but glucose reabsorption in this segment failed to increase further and overt glycosuria eventually developed. Thus the intermediate segment possesses some capacity to reabsorb glucose when glucose load is increased, and glycosuria develops only when the glucose reabsorptive capacity of this segment is exceeded. We conclude that the intermediate segment serves as the "buffer zone" of renal glucose transport and plays an important role in the regulation of urinary glucose excretion.