We studied the effects of acute diabetes mellitus on jejunal transport of phosphate (32P) by rat brush border membrane vesicles (BBMV) using a Millipore filtration technique. Diabetes was induced by an intravenous (i.v.) injection of 50 mg/kg of streptozocin (STZ). Control and diabetic rats were studied 4 days after the induction of diabetes. In both control and diabetic rats, the presence of a sodium gradient significantly enhanced the uptake of 32P at 20 s and at 1, 2, 5, and 60 min as compared with potassium gradient conditions. Na+-dependent 32P uptake at 20 s and at 1 and 2 min was significantly greater in the diabetic BBMV compared with controls. Na+-independent 32P uptake in both diabetic and control BBMV was similar. To determine whether the enhancement of Na+-dependent 32P uptake in diabetic BBMV is due to an induction of Na+ /phosphate cotransporter activity, or a change in Na+ permeability, two additional studies were conducted. Trans-stimulation studies nullifying all electrochemical gradients across the membranes were performed. In diabetic BBMV, 32P uptake at all time points was significantly greater than corresponding values in controls, indicating an increase in the activity of Na+ /phosphate cotransporters. 22Na uptake into BBMV at 30 s and at 1, 2, and 60 min was not different between diabetics and controls, indicating that Na+ permeability is not altered in diabetes. Furthermore, kinetic studies using phosphate concentrations between 0.05 and 2.5 mM indicate a significant increase in Vmax capacity of diabetic rats compared with controls without a change in Km values. We conclude that the reason for the increased uptake of 32P observed in 4-day diabetic BBMV is due to an increase in the activity of the Na+ /phosphate cotransporter.

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