Renal adaptation to low-phosphate diet in diabetic rats

Insulin stimulates the Na(+)-Pi 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 Pi. It has been proposed that insulin may play a role in the rapid renal adaptation to dietary deprivation of Pi. 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 Pi diet or a low Pi diet for 3 days. At the end of the third day, BBM vesicles were prepared from renal cortex and Na(+)-Pi cotransport was measured. At the whole kidney level, diabetic rats showed a normal adaptive response. There was a prompt and marked decrease in urinary Pi excretion when the rats ate a low Pi diet. At the BBM level, however, the adaptive response was absent. There was no increase in Na(+)-Pi cotransport in diabetic rats fed low Pi diet. Treatment of diabetic rats with exogenous insulin before feeding low Pi diet restored the adaptive increase in Pi transport by BBM. Insulin appears to be required for the adaptation of proximal tubule Pi transport to low Pi diet. In the absence of this adaptation in proximal tubule BBM, a compensatory response in the kidney may produce an increase in Pi reabsorption in later segments of the nephron.