Kim Dongun, Sands Jeff M, Klein Janet D
Emory Univ. School of Medicine, Renal Division, WMRB Rm. 338, 1639 Pierce Drive NE, Atlanta, GA 30322, USA.
Am J Physiol Renal Physiol. 2004 Apr;286(4):F760-6. doi: 10.1152/ajprenal.00369.2003. Epub 2003 Nov 25.
In rats with streptozotocin-induced diabetes mellitus for 10-20 days, we showed that the abundance of the major medullary transport proteins involved in the urinary concentrating mechanism, urea transporter (UT-A1), aquaporin-2 (AQP2), and the Na+-K+-2Cl- cotransporter (NKCC2/BSC1), is increased, despite the ongoing osmotic diuresis. To test whether vasopressin is necessary for these diabetes mellitus-induced changes in UT-A1, AQP2, or NKCC2/BSC1, we studied Brattleboro rats because they lack vasopressin. Brattleboro rats were given vasopressin (2.4 microg/day via osmotic minipump) for 5 or 12 days. At 5 days, vasopressin increased AQP2 protein abundance but decreased UT-A1 abundance compared with untreated Brattleboro rats. At 12 days, vasopressin increased the abundance of both UT-A1 and AQP2 proteins but did not alter NKCC2/BSC1. Next, untreated Brattleboro rats were made diabetic for 10 days by injecting them with streptozotocin (40 mg/kg). Diabetes mellitus increased the abundance of AQP2 and NKCC2/BSC1 proteins, but UT-A1 protein abundance did not increase. Third, vasopressin-treated Brattleboro rats were made diabetic with streptozotocin for 10 days. In vasopressin-treated Brattleboro rats, diabetes mellitus increased UT-A1, AQP2, and NKCC2/BSC1 protein abundances. Vasopressin significantly increased UT-A1 phosphorylation in vasopressin-treated diabetic Brattleboro rats but not in the other groups of Brattleboro rats. We conclude that 1) administering vasopressin to Brattleboro rats for 12 days, but not for 5 days, increases UT-A1 protein abundance and 2) vasopressin is necessary for the increase in UT-A1 protein in diabetic rats but is not necessary for the increase in AQP2 or NKCC2 proteins.
在链脲佐菌素诱导的糖尿病大鼠模型中，造模10 - 20天，我们发现尽管存在渗透性利尿，但参与尿液浓缩机制的主要髓质转运蛋白，尿素转运体（UT - A1）、水通道蛋白2（AQP2）和钠 - 钾 - 2氯协同转运蛋白（NKCC2/BSC1）的丰度却增加了。为了检测血管加压素对于UT - A1、AQP2或NKCC2/BSC1这些糖尿病诱导变化是否必要，我们研究了遗传性尿崩症大鼠（Brattleboro大鼠），因为它们缺乏血管加压素。给Brattleboro大鼠通过渗透微型泵给予血管加压素（2.4微克/天），持续5天或12天。在5天时，与未处理的Brattleboro大鼠相比，血管加压素增加了AQP2蛋白丰度，但降低了UT - A1丰度。在12天时，血管加压素增加了UT - A1和AQP2蛋白的丰度，但未改变NKCC2/BSC1。接下来，给未处理的Brattleboro大鼠注射链脲佐菌素（40毫克/千克）使其糖尿病10天。糖尿病增加了AQP2和NKCC2/BSC1蛋白的丰度，但UT - A1蛋白丰度未增加。第三，给经血管加压素处理的Brattleboro大鼠注射链脲佐菌素使其糖尿病10天。在经血管加压素处理的Brattleboro糖尿病大鼠中，糖尿病增加了UT - A1、AQP2和NKCC2/BSC1蛋白的丰度。血管加压素显著增加了经血管加压素处理的糖尿病Brattleboro大鼠中UT - A1的磷酸化水平，但在其他组的Brattleboro大鼠中未增加。我们得出结论：1）给Brattleboro大鼠给予血管加压素12天而非5天会增加UT - A1蛋白丰度；2）血管加压素对于糖尿病大鼠中UT - A1蛋白的增加是必要的，但对于AQP2或NKCC2蛋白的增加不是必要的。
