Ottlecz A, Garcia C A, Eichberg J, Fox D A
College of Optometry, University of Houston, TX 77204-6052.
Curr Eye Res. 1993 Dec;12(12):1111-21. doi: 10.3109/02713689309033509.
The temporal pattern of changes in the specific activities of retinal Na+, K(+)-ATPase (Na, K-ATPase) and Mg(2+)-ATPase (Mg-ATPase) were determined at several time intervals following the onset of diabetes in streptozotocin-induced diabetic (STZ: at 1, 2, 4 and 6 months) Long-Evans hooded rats, spontaneously diabetic Zucker diabetic fatty (ZDF: at 1, 2 and 4 months) rats and their age-matched controls. These animals were utilized as models for insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM), respectively. Na, K-ATPase specific activity, using 10(3) M ouabain, was decreased (-6% to -14%) at all time points after the appearance of hyperglycemia in the ZDF rat, but was reduced only after 4 and 6 months in the STZ rat (-8% and -14%, respectively). In contrast, Mg-ATPase activity was significantly increased (13%) after 4 months in the ZDF rat and after 6 months in the STZ rat (8%). The concentration-dependent inhibitory effects of ouabain (10(-9) to 10(-3) M) on the activity of Na, K-ATPase in diabetic rats and age-matched controls was used to assess the time-dependent effects of diabetes on the alpha 3-high ouabain affinity or the alpha 1-low ouabain affinity retinal Na, K-ATPase isozymes. The retinal Na, K-ATPase activity for the alpha 3 isozyme was significantly lower at all times examined for the ZDF (-5% to -26%) and STZ-induced diabetic rats (-8% to -14%). This was reflected in the markedly decreased half-maximal inhibitory concentrations (IC50) of ouabain for the alpha 3 isozyme. For example, after four months of diabetes, the mean +/- SEM IC50 values were 12 +/- 3 nM in the STZ rats and 48 +/- 6 nM in the age-matched controls and 19 +/- 3 nM in the ZDF rats and 30 +/- 4 nM in the age-matched controls. In contrast, the activity of the alpha 1 isozyme was slightly, but significantly, decreased at 2 and 4 months in the ZDF rats (-4% to -7%) and after 4 and 6 months in the STZ-induced diabetic rats (-3% to -9%) while the IC50 values were unchanged. Moreover, the Hill coefficient for the alpha 3 isozyme was decreased in both diabetic groups while it was unchanged for the alpha 1 isozyme.(ABSTRACT TRUNCATED AT 400 WORDS)
在链脲佐菌素诱导的糖尿病（STZ：1、2、4和6个月）Long-Evans带帽大鼠、自发性糖尿病Zucker糖尿病肥胖（ZDF：1、2和4个月）大鼠及其年龄匹配的对照大鼠中，在糖尿病发病后的几个时间间隔测定视网膜Na⁺、K⁺-ATP酶（Na，K-ATP酶）和Mg²⁺-ATP酶（Mg-ATP酶）比活性的时间变化模式。这些动物分别用作胰岛素依赖型糖尿病（IDDM）和非胰岛素依赖型糖尿病（NIDDM）的模型。在ZDF大鼠出现高血糖后的所有时间点，使用10³M哇巴因测定的Na，K-ATP酶比活性均降低（-6%至-14%），但在STZ大鼠中仅在4个月和6个月后降低（分别为-8%和-14%）。相反，ZDF大鼠在4个月后和STZ大鼠在6个月后Mg-ATP酶活性显著增加（13%和8%）。使用哇巴因（10⁻⁹至10⁻³M）对糖尿病大鼠和年龄匹配对照中Na，K-ATP酶活性的浓度依赖性抑制作用，来评估糖尿病对α3-高哇巴因亲和力或α1-低哇巴因亲和力视网膜Na，K-ATP酶同工酶的时间依赖性影响。在ZDF（-5%至-26%）和STZ诱导的糖尿病大鼠（-8%至-14%）中，在所有检测时间点，α3同工酶的视网膜Na，K-ATP酶活性均显著降低。这反映在哇巴因对α3同工酶的半数最大抑制浓度（IC50）明显降低。例如，糖尿病4个月后，STZ大鼠的平均±SEM IC50值为12±3 nM，年龄匹配对照为48±6 nM；ZDF大鼠为19±3 nM，年龄匹配对照为30±4 nM。相反，ZDF大鼠在2个月和4个月时α1同工酶活性略有但显著降低（-4%至-7%），STZ诱导的糖尿病大鼠在4个月和6个月后降低（-3%至-9%），而IC50值不变。此外，两个糖尿病组中α3同工酶的希尔系数均降低，而α1同工酶的希尔系数不变。（摘要截断于400字）
