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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Satake
Masako
M
Department of Clinical Pharmacokinetics, Hoshi University, Shinagawa-ku, Tokyo 142-8501, Japan.
Ikarashi
Nobutomo
N
Ichikawa
Yuhei
Y
Maniwa
Ayaka
A
Toda
Takahiro
T
Ito
Kiyomi
K
Ochiai
Wataru
W
Sugiyama
Kiyoshi
K
D000818:Animals; D051399:Aquaporin 2 / Q000235:genetics / Q000502:physiology*; D001786:Blood Glucose / Q000187:drug effects; D015153:Blotting, Western; D003681:Dehydration / Q000209:etiology / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008297:Male; D051379:Mice; D011141:Polyuria / Q000150:complications* / Q000209:etiology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014667:Vasopressins / Q000235:genetics*
C496024:Aqp2 protein, mouse; D051399:Aquaporin 2; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D012333:RNA, Messenger; D014667:Vasopressins