The role of renal aquaporin 2 in the alleviation of dehydration associated with diabetic polyuria in KKAy mice

• Published in: Life sciences (1973) 2010-10, Vol.87 (15), p.475-480
• Main Authors: Satake, Masako, Ikarashi, Nobutomo, Ichikawa, Yuhei, Maniwa, Ayaka, Toda, Takahiro, Ito, Kiyomi, Ochiai, Wataru, Sugiyama, Kiyoshi
• Format: Article
• Language: English
• Subjects: Animals; Aquaporin 2; Aquaporin 2 - genetics; Aquaporin 2 - physiology; Blood Glucose - drug effects; Blotting, Western; Dehydration - etiology; Dehydration - genetics; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Disease Models, Animal; Gene Expression Regulation; Hypoglycemic Agents - pharmacology; Insulin - pharmacology; Kidney; KKAy mice; Male; Mice; Polyuria - complications; Polyuria - etiology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Type 2 diabetes; Vasopressin; Vasopressins - genetics
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2010.09.001

Polyuria is a symptom that appears in association with diabetes mellitus. Because sustained polyuria causes serious dehydration, it is believed that the body has a compensating mechanism to alleviate dehydration. In the present study, the role of renal aquaporin 2 (AQP2) in the compensating mechanism was investigated in KKAy mice, a type 2 diabetes model. The renal AQP2 expression levels in KKAy mice aged between 5 and 24 weeks were determined using Western blotting. The hypothalamic vasopressin mRNA expression levels also were measured by real-time RT-PCR. Insulin was subcutaneously administered to 11-week-old KKAy mice twice a day for 7 days. After insulin treatment, the renal AQP2 protein expression and the hypothalamic vasopressin mRNA expression were measured. The urinary volumes of 5- and 12-week-old KKAy mice were 1.5 ± 0.3 mL and 9.5 ± 1.2 mL, respectively. The inner medullary AQP2 protein expression of 12-week-old KKAy mice was approximately 2.5-fold higher than that of 5-week-old KKAy mice. The hypothalamic vasopressin mRNA expression of 12-week-old KKAy mice was approximately twice that of 5-week-old KKAy mice. Insulin treatment in KKAy mice resulted in a significant reduction in the plasma glucose level, urinary volume, and inner medullary AQP2 protein and hypothalamic vasopressin mRNA expression. The present study demonstrated that AQP2 is a renal functional molecule of vasopressin that controls urinary volume and that AQP2 in the kidney increases to alleviate dehydration due to type 2 diabetes with polyuria.