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

Abstract

In diabetes mellitus, water turnover in the body is enhanced because of the glucose-induced osmotic diuresis and it is usually assumed that the concentrating capacity of the kidney is partially impaired. On the other hand, plasma vasopressin concentration is known to be increased by several fold in patients with Type I (insulin-dependent) diabetes mellitus or Type II (non-insulin-dependent) diabetes mellitus as well as in animal models of experimental or genetic diabetes mellitus [1±6]. This high vasopressin concentration is accompanied by a desensitization of V1 a receptors in liver, kidney and platelets [7,8]. In contrast, renal V2 receptors, responsible for the antidiuretic action of the hormone, are not down-regulated [8].Actually, higher vasopressin in diabetes mellitus probably represents an appropriate adaptation by limiting to some extent the amount of water required Abstract Aims/hypothesis. 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. Methods. 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. Results. In these rats, glycaemia, urine flow rate and water reabsorption were respectively fourfold, ninefold 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. Conclusion/interpretation. 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. [Diabetologia (2001) 44: 637±645]

Increases in the Expression Levels of Aquaporin-2 and Aquaporin-3 in the Renal Collecting Tubules Alleviate Dehydration Associated with Polyuria in Diabetes Mellitus

“…[5][6][7] The results of this study strongly suggest that the increased expression levels of AQP2 and AQP3 can promote the re-absorption of water and play a role as a compensatory mechanism to complement the reduction of water content in the body. In diabetes patients, although a significant decrease in body water due to polyuria has been a concern, there have been few actual cases of dehydration.…”

“…3,4) Enhanced expression of renal AQP2 has been reported when polyuria occurs in streptozotocin (STZ)-induced type I diabetes model mice. 5,6) In addition, we previously found that the level of renal AQP2 expression increases along with the pathological progression of type II diabetes mellitus using KKAy mice, the animal model of type II diabetes. 7) Although this increased AQP2 expression in the kidneys has been regarded as a possible compensatory mechanism to alleviate dehydration in polyuria, the physiological significance of the increase in renal AQP2 expression in diabetes remains unknown.…”

Changes in renal medullary transport proteins during uncontrolled diabetes mellitus in rats

“…We previously showed that at 3 days of diabetes, UT-A1 protein abundance is downregulated in the IM tip, compared with control rats (9), and the present study shows that UT-A1 protein is downregulated in the IM tip at 5 days. In contrast, Bardoux and colleagues (1) showed that at 21 days post-STZ treatment, diabetic rats show an increase in UT-A1 mRNA and protein in the IM base. In particular, they showed that the 117-kDa band was increased without a change in the 97-kDa band (1).…”

Diabetic rats present higher urinary loss of proteins and lower renal expression of megalin, cubilin, ClC-5, and CFTR

“…Maintenance of a high glucose load along the whole length of the renal tubules stimulates osmotic diuresis, with increased urinary flow (Bardoux et al. 2001; Katsuno et al. 2007).…”