Aquaporin-2 and urea transporter-A1 are up-regulated in rats with type I diabetes mellitus.

Abstract

Although the urine flow rate is considerably higher in diabetes mellitus, water reabsorption is greatly increased to concentrate an increased amount of solutes. Our study evaluated the expression of aquaporins and urea transporters, which are essential to the urinary concentration process. Northern blot and immunoblot were used to quantify mRNA and proteins for aquaporin-2 (AQP2) as well as urea transporters UT-A1, UT-A2 and UT-B1, in subzones of the renal medulla of rats with streptozotocin-induced diabetes. In these rats, glycaemia, urine flow rate and water reabsorption were respectively fourfold, nine-fold and fourfold those of control rats. The AQP2 protein isoforms were significantly up-regulated in outer and inner medulla. In the base and tip of inner medulla, UT-A1 mRNA was significantly up-regulated (three- and 1.3-fold, respectively) as well as the 117 kD protein (ten- and threefold, respectively) whereas the 97 kD protein was not changed or decreased twofold, respectively. This suggests that, in diabetes, the inner medullary collecting duct is endowed with more UT-A1, especially in its initial part. In the case of mRNA and proteins of UT-A2, located in thin descending limbs in the inner stripe of outer medulla, they were respectively not changed and down-regulated in diabetic rats. This study shows that in diabetes, the increased expression of AQP2 and UT-A1 in medullary collecting duct is consistent with an improved concentrating activity. In addition, the underexpression of UT-A2 and the overexpression of UT-A1 in the initial medullary collecting duct are reminiscent of the changes seen after experimental reduction of urine concentration or low protein feeding.