Simmons D A, Winegrad A I
Department of Medicine, School of Medicine, University of Pennsylvania, Philadelphia.
Diabetologia. 1989 Jul;32(7):402-8. doi: 10.1007/BF00271258.
Hyperglycaemia decreases (Na+, K+)-ATPase activity in specific tissues by a mechanism whose effects are prevented by aldose reductase inhibitors and by raising plasma myo-inositol. This mechanism was activated and studied in vitro in normal rabbit aortic intima-media. Raising medium glucose to 10 mmol/l for 60 min inhibited a major component of (Na+, K+)-ATPase-mediated 86Rb+/K+ uptake normally operative in resting aortic intima-media in medium containing normal plasma levels of glucose (5 mmol/l) and myo-inositol (70 mumol/l); 20 or 30 mmol/l glucose had no greater effect. This effect occurred under conditions in which the aortic intima-media's normal myo-inositol content is not detectably decreased. The inhibition was prevented by sorbinil (10 mumol/l) and by raising medium myo-inositol from 70 to 500 mumol/l, which had no effect on (Na+, K+)-ATPase activity when the medium glucose remained at 5 mmol/l. Raising medium glucose selectively inhibited a component of (Na+, K+)-ATPase activity that requires medium myo-inositol, because it is maintained by a regulatory system through rapid basal phosphatidylinositol turnover in a discrete pool, which is replenished by a fraction of basal de novo phosphatidylinositol synthesis that is selectively dependent on myo-inositol uptake. Medium myo-inositol at a normal plasma level became inadequate to maintain this fraction of basal de novo phosphatidylinositol synthesis [( 1,3-14C]glycerol incorporation) when the medium glucose was raised. When sorbinil was added raising medium glucose did not alter the ability of 70 mumol/l medium myoinositol to maintain the (Na+, K+)-ATPase activity that requires medium myo-inositol.(ABSTRACT TRUNCATED AT 250 WORDS)
高血糖通过一种机制降低特定组织中的（钠，钾）-ATP酶活性，醛糖还原酶抑制剂和提高血浆肌醇可阻止该机制的作用。此机制在体外正常兔主动脉内膜-中膜中被激活并进行研究。将培养基葡萄糖浓度提高到10 mmol/L持续60分钟，可抑制（钠，钾）-ATP酶介导的86Rb+/K+摄取的一个主要成分，该摄取在含有正常血浆葡萄糖水平（5 mmol/L）和肌醇（70 μmol/L）的培养基中，对静息主动脉内膜-中膜通常起作用；20或30 mmol/L葡萄糖的作用并无更强。这种作用发生在主动脉内膜-中膜正常肌醇含量未检测到降低的情况下。索比尼尔（10 μmol/L）以及将培养基肌醇从70 μmol/L提高到500 μmol/L可阻止这种抑制，当培养基葡萄糖保持在5 mmol/L时，这对（钠，钾）-ATP酶活性没有影响。提高培养基葡萄糖选择性抑制了（钠，钾）-ATP酶活性的一个成分，该成分需要培养基肌醇，因为它由一个调节系统维持，该调节系统通过离散池中快速的基础磷脂酰肌醇周转实现，基础从头合成磷脂酰肌醇的一部分选择性依赖肌醇摄取来补充该离散池。当培养基葡萄糖升高时，正常血浆水平的培养基肌醇不足以维持基础从头合成磷脂酰肌醇的这一部分（[1,3-14C]甘油掺入）。当添加索比尼尔时，提高培养基葡萄糖不会改变70 μmol/L培养基肌醇维持需要培养基肌醇的（钠，钾）-ATP酶活性的能力。（摘要截断于250字）
