Both
insulin deficiency and
glycosuria are known to inhibit the tubular reabsorption of
phosphate. This inhibition has previously been evaluated either in the fasted state or on a normal
phosphate diet. The goal of this study was to evaluate how dietary
phosphate depletion affected the relative effects of
insulin deficiency and
glycosuria on the tubular reabsorption of
phosphate. Rats were maintained on either a low- (0.03%) or normal (0.8%)
phosphate diet. After 5 days, one half of the animals in each group received
streptozotocin to induce short-term
insulin deficiency, whereas the other half received vehicle alone. Two days later,
sodium-dependent
phosphate uptake by renal brush border membrane vesicles (BBMV) was evaluated in each of the four experimental groups. The effect of
glucose on
phosphate uptake was determined by the addition of varying concentrations of
glucose (between 0 and 32 mmol/L) to the extravesicular transport fluid. BBMV
phosphate uptake was about threefold higher in the nondiabetic rats fed a low-
phosphate diet as compared with the nondiabetic animals maintained on a normal
phosphate diet. In rats maintained on a low-
phosphate diet,
streptozotocin treatment prevented the increase in BBMV
phosphate transport; in contrast, in animals fed a normal
phosphate diet,
streptozotocin treatment had no effect on BBMV
phosphate transport. Extravesicular
glucose significantly inhibited
phosphate transport in a dose-related manner, regardless of dietary
phosphate or
insulin status. Because fasting mimics the catabolic state associated with
insulin deficiency, BBMV
phosphate transport was also measured in rats fasted for 48 h after the administration of
streptozotocin or vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)