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

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Enhanced expression of renal aquaporin-2 (AQP2) has been reported when polyuria occurs in diabetic animal models. The purpose of this study was to clarify the possibility that increased AQP2 expression in the kidneys play a role as a compensatory mechanism to alleviate diabetic dehydration. Lithium carbonate (Li₂CO₃), which decreases the renal expression of AQPs, was administered to streptozotocin (STZ)-induced model mice of type I diabetes mellitus (STZ mice), to investigate the relationship between urine volume and renal AQP expression. Plasma glucose and urine glucose levels were similar between STZ mice given feed containing Li₂CO₃ for 10 d and un-treated STZ mice. Urine volume increased to 70 ml/d for the Li₂CO₃-treated STZ mice, compared to 36 ml/d for un-treated STZ mice. No changes were observed in creatinine clearance or the mRNA expression levels of sodium myo-inositol transporter and taurine transporter, which are genes associated with the regulation of osmotic pressure in the kidney, in the Li₂CO₃-treated STZ mice relative to un-treated STZ mice. Protein expression levels of AQP2 and aquaporin-3 (AQP3) of the renal inner medulla were significantly decreased in the Li₂CO₃-treated STZ mice, compared to levels in the STZ group. This study revealed that the decreased expression levels of AQP2 and AQP3 in the kidney increased the urine volume in mice without a change in urinary osmotic pressure. The results of this study suggest that the increased renal AQP2 and AQP3 expression, in the setting of polyuria, physiologically serves as a compensatory mechanism to alleviate dehydration in diabetes mellitus.