Effect of myo-inositol on renal Na-K-ATPase in experimental diabetes.
Effect of myo-inositol on renal Na-K-ATPase in experimental diabetes.
复制标题
肌醇对实验性糖尿病肾 Na-K-ATP 酶的影响。
DOI：
10.1016/0026-0495(90)90161-5
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Epstein,FH
中科院分区：
文献类型：
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作者：
Cohen,RA;MacGregor,LC;Spokes,KC;Silva,P;Epstein,FH
实验性糖尿病大鼠肾脏Na-K-ATP酶活性增高。由于肾脏富含肌醇，且肌醇代谢异常与糖尿病早期神经系统并发症有关，本实验采用链脲佐菌素（STZ）诱导SD大鼠糖尿病模型，观察了肌醇（650 mg/kg）灌胃给药对糖尿病大鼠肾脏髓质和皮质匀浆Na ~+-K ~+-ATP酶活性的影响。糖尿病大鼠1周时延髓Na-K-ATP酶（μmol/mg蛋白/h）较对照组增加约60%（25.9 ± 0.07 v16.3 ± 0.7;P<0.01）。尽管持续高血糖，但补充肌醇完全阻止了这种增加。在2周时，观察到类似的结果;与对照组相比，糖尿病大鼠的延髓Na-K-ATP酶活性增加了50%，并且肌醇再次阻止了这种增加。还通过管饲法（20 mg/kg）给予Sorbinil（醛糖还原酶抑制剂）2周，并部分阻止了髓质Na-K-ATP酶活性的增加（20.0 ± 0.9;P<0.05）。在第7天和第14天，未治疗的糖尿病大鼠皮层Na-K-ATP酶活性也显著高于非糖尿病对照组大鼠，肌醇或Sorbinil可阻止这种增加，肌醇或Sorbinil不降低非糖尿病对照组大鼠的Na-K-ATP酶活性，它们也不能阻止单肾切除术后代偿性肥大中髓质Na-K-ATP酶的增加。外髓质的肌醇含量约为皮质的五至六倍，但不受糖尿病状态的影响。补充肌醇对Na-K-ATP酶的影响似乎与肾小球滤过率（GFR）无关，因为糖尿病大鼠菊粉清除率的增加（0.63 ± 0.05 mL/min/100 g vs0.42 ± 0.04）不受肌醇的影响。结果表明，肌醇代谢紊乱可能在糖尿病引起的肾脏变化中发挥作用。
The activity of Na-K-ATPase in the kidney is increased by experimental diabetes. Because the kidney is rich inmyo-inositol and abnormal inositol metabolism has been implicated in early neural complications of diabetes, we studied the effect ofmyo-inositol supplementation on Na-K-ATPase activity in renal medullary and cortical homogenates of Sprague-Dawley rats made diabetic with streptozotocin.Myo-inositol (650 mg/kg) was administered by gavage daily for 1 and 2 weeks after induction of diabetes. Medullary Na-K-ATPase (μmol/mg protein/h) was increased at 1 week by approximately 60% in diabetic rats versus control (25.9 ± 0.07v16.3 ± 0.7;P< .01). This increase was completely prevented bymyo-inositol supplementation, despite persistent hyperglycemia. At 2 weeks, similar results were seen; medullary Na-K-ATPase activity was increased by 50% in diabetic rats compared with control, and once againmyo-inositol prevented this increase. Sorbinil, the aldose reductase inhibitor, was also administered by gavage (20 mg/kg) for 2 weeks and partially prevented the increase in medullary Na-K-ATPase activity (20.0 ± 0.9;P< .05). At both 7 and 14 days, Na-K-ATPase activity in the cortex of untreated diabetic rats was also significantly increased compared with nondiabetic control rats and the increase was prevented bymyo-inositol or Sorbinil.Myo-inositol or Sorbinil did not reduce Na-K-ATPase activity of nondiabetic control rats, nor did they prevent the increase in medullary Na-K-ATPase in compensatory hypertrophy following uninephrectomy.Myo-inositol content of outer medulla was about five to six times that of cortex, but was unaltered by the diabetic state. The effect ofmyo-inositol supplements on Na-K-ATPase appeared independent of glomerular filtration rate (GFR), since the increase in inulin clearance measured in diabetic rats (0.63 ± 0.05 mL/min/100 g v 0.42 ± 0.04 in controls) was unaffected bymyo-inositol. The results indicate that disturbed inositol metabolism may play a role in the renal changes produced by diabetes.