Urine concentration in the diabetic mouse requires both urea and water transporters

作者：Ilori Titilayo O^*; Blount Mitsi A; Martin Christopher F; Sands Jeff M; Klein Janet D

来源：American Journal of Physiology - Renal Fluid and Electrolyte Physiology, 2013, 304(1): F103-F111.

DOI：10.1152/ajprenal.00385.2012

• urea transporter-A1/A3 knockout
• diabetes
• aquaporin-2
• phosphorylated serine-256-aquaporin-2
• phosphorylated serine-486-urea transporter-A1
• vasopressin

Ilori TO, Blount MA, Martin CF, Sands JM, Klein JD. Urine concentration in the diabetic mouse requires both urea and water transporters. Am J Physiol Renal Physiol 304: F103-F111, 2013. First published November 7, 2012; doi:10.1152/ajprenal.00385.2012.-The regulation of the inner medullary collecting duct (IMCD) urea transporters (UT-A1, UT-A3) and aquaporin-2 (AQP2) and their interactions in diabetic animals is unknown. We investigated whether the urine concentrating defect in diabetic animals was a function of AQP2, the UT-As, or both transporters. UT-A1/UT-A3 knockout (UT-A1/A3 KO) mice produce dilute urine. We gave wild-type (WT) and UT-A1/A3 KO mice vasopressin via minipump for 7 days. In WT mice, vasopressin increased urine osmolality from 3,000 to 4,550 mosmol/kgH(2)O. In contrast, urine osmolality was low (800 mosmol/kgH(2)O) in the UT-A1/A3 KOs and remained low following vasopressin. Surprisingly, AQP2 protein abundance increased in UT-A1/A3 KO (114%) and WT (92%) mice. To define the role of UT-A1 and UT-A3 in the diabetic responses, WT and UT-A1/A3 KO mice were injected with streptozotocin (STZ). UT-A1/A3 KO mice showed only 40% survival at 7 days post-STZ injection compared with 70% in WT. AQP2 did not increase in the diabetic UT-A1/A3 KO mice compared with a 133% increase in WT diabetic mice. Biotinylation studies in rat IMCDs showed that membrane accumulation of UT-A1 increased by 68% in response to vasopressin in control rats but was unchanged by vasopressin in diabetic rat IMCDs. We conclude that, even with increased AQP2, UT-A1/UT-A3 is essential to optimal urine concentration. Furthermore, UT-A1 may be maximally membrane associated in diabetic rat inner medulla, making additional stimulation by vasopressin ineffective.

• 出版日期2013-1