RENAL ADAPTATION TO LOW-PHOSPHATE DIET IN DIABETIC RATS

Insulin stimulates the Na+-P(i) cotransport system in the brush-border membrane (BBM) of the renal proximal tubule, and an acute decrease in plasma insulin leads to a decrease in renal reabsorption of P(i). It has been proposed that insulin may play a role in the rapid renal adaptation to dietary deprivation of P(i). This hypothesis was tested using rats with low plasma insulin due to streptozotocin-induced diabetes. Both control and diabetic rats were housed in metabolic cages and fed either a normal P(i) diet or a low P(i) diet for 3 days. At the end of the third day, BBM vesicles were prepared from renal cortex and Na+-P(i) cotransport was measured. At the whole kidney level, diabetic rats showed a normal adaptive response. There was a prompt and marked decrease in urinary P(i) excretion when the rats ate a low P(i) diet. At the BBM level, however, the adaptive response was absent. There was no increase in Na+-P(i) cotransport in diabetic rats fed low P(i) diet. Treatment of diabetic rats with exogenous insulin before feeding low P(i) diet restored the adaptive increase in P(i) transport by BBM. Insulin appears to be required for the adaptation of proximal tubule P(i) transport to low P(i) diet. In the absence of this adaptation in proximal tubule BBM, a compensatory response in the kidney may produce an increase in P(i) reabsorption in later segments of the nephron.