Ku D D, Sellers B M, Meezan E
Endocrinology. 1986 Aug;119(2):672-9. doi: 10.1210/endo-119-2-672.
The effects of experimental diabetes on renal tubular Na,K-ATPase activity were measured 4, 7, 14, 21, 28, and 56 days after ip injection of streptozotocin (STZ; 60 mg/kg) in rats. Significant increases in serum and urinary glucose levels as well as urinary volume and electrolyte output were observed 24 h after STZ injection. The elevated serum and urinary glucose levels were maintained during the entire 8-week experimental period, while urinary volume and electrolyte output showed an initial rising phase, reaching a peak at approximately 2-3 weeks, followed by a stabilization phase at a level lower than the peak effect, but still significantly higher than that in the saline-citrate-treated controls. A significant increase (+25.3%) in renal outer medullary Na,K-ATPase activity was observed 4 days after the induction of STZ-diabetes, while similar increases were not observed in the cortical regions until after 7 days of experimental diabetes. These elevated renal cortical and outer medullary enzyme activities, however, were subsequently maintained during the entire 8-week experimental period. In addition, a similar time course of development of renal hypertrophy, as indicated by increases in kidney weights and kidney protein to DNA ratios, was observed after the induction of STZ-diabetes in rats. Therefore, the present data indicate that renal hypertrophy and increased renal Na,K-ATPase develop early and with a similar time course after induction of STZ diabetes in rats and may mediate the gradual amelioration of excessive renal electrolyte loss seen in this experimental condition. Since Na,K-ATPase-mediated ion transport is the major consumer of metabolic energy in the kidney and is centrally important to renal function, it is suggested that the early and pronounced increase in renal Na,K-ATPase seen in diabetes is an essential component of the renal hypertrophy and hyperfunction seen in this disease and may represent an important adaptive change in the kidneys in response to glucose osmotic diuresis in the experimental diabetic animals.
在大鼠腹腔注射链脲佐菌素（STZ；60 mg/kg）后的第4、7、14、21、28和56天，测量实验性糖尿病对肾小管钠钾ATP酶活性的影响。注射STZ后24小时，观察到血清和尿葡萄糖水平以及尿量和电解质排出量显著增加。在整个8周的实验期内，血清和尿葡萄糖水平持续升高，而尿量和电解质排出量呈现出一个初始上升阶段，在大约2 - 3周时达到峰值，随后进入稳定阶段，稳定在低于峰值效应的水平，但仍显著高于柠檬酸盐生理盐水处理的对照组。在诱导STZ糖尿病4天后，观察到肾外髓质钠钾ATP酶活性显著增加（+25.3%），而在实验性糖尿病7天后，皮质区域才出现类似的增加。然而，这些升高的肾皮质和外髓质酶活性在整个8周的实验期内随后得以维持。此外，在大鼠诱导STZ糖尿病后，观察到肾脏重量增加以及肾脏蛋白质与DNA比值升高所表明的肾肥大发展的类似时间进程。因此，目前的数据表明，在大鼠诱导STZ糖尿病后，肾肥大和肾钠钾ATP酶增加在早期出现且具有相似的时间进程，并且可能介导了在此实验条件下所见的肾脏电解质过度丢失的逐渐改善。由于钠钾ATP酶介导的离子转运是肾脏代谢能量的主要消耗者，并且对肾功能至关重要，因此提示糖尿病中早期且显著增加的肾钠钾ATP酶是该疾病中所见肾肥大和肾功能亢进的重要组成部分，并且可能代表了实验性糖尿病动物肾脏对葡萄糖渗透性利尿的重要适应性变化。
