Phosphate Transport by Jejunal Brush Border Membrane Vesicles of the Streptozocin-diabetic Rat

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 V_max capacity of diabetic rats compared with controls without a change in K_m 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.