Suzuki K, Kawamura T, Sakakibara F, Sasaki H, Sano T, Sakamoto N, Hotta N
3rd Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Diabet Med. 1999 Jan;16(1):67-73. doi: 10.1046/j.1464-5491.1999.00022.x.
To investigate the influence of glucose and the efficacy of two different aldose reductase (AR) inhibitors, epalrestat and SNK-860, on the polyol pathway and myo-inositol metabolism in human neutrophils.
We incubated neutrophils with various concentrations of glucose and AR inhibitors. The neutrophils from healthy volunteers were incubated in the media containing 5-40 mmol/l glucose with or without an AR inhibitor. The sorbitol and myo-inositol contents, and myo-inositol uptake were measured by high performance liquid chromatography and radio isotope technique with 2-[3H]-myo-inositol.
After 2 h incubation, the sorbitol content increased with rising extracellular glucose concentrations, while the myo-inositol content decreased. Both AR inhibitors reduced the sorbitol content in neutrophils exposed to 40 mmol/l glucose medium. A 70% fall in the myo-inositol content in neutrophils exposed to 40mmol/glucose medium was attenuated approximately 40% by the addition of AR inhibitors. myo-Inositol uptake into neutrophils was inhibited by high glucose. AR inhibitors significantly ameliorated the decrease in myo-inositol uptake, but did not completely normalize it.
Our present in vitro studies showed that the glucose-induced metabolic alterations in human neutrophils were similar to those in tissues prone to diabetic complications, and that AR inhibitors effectively corrected glucose-induced imbalances of the polyol pathway and myo-inositol uptake in neutrophils. In addition, our study suggests that glucose-induced metabolic alterations may result in the neutrophil dysfunction and that an AR inhibitor may be capable ameliorating it.
研究葡萄糖以及两种不同的醛糖还原酶（AR）抑制剂依帕司他和SNK-860对人中性粒细胞多元醇途径和肌醇代谢的影响及疗效。
我们将中性粒细胞与不同浓度的葡萄糖和AR抑制剂一起孵育。来自健康志愿者的中性粒细胞在含有5 - 40 mmol/L葡萄糖且有或没有AR抑制剂的培养基中孵育。采用高效液相色谱法和用2-[3H]-肌醇的放射性同位素技术测定山梨醇和肌醇含量以及肌醇摄取量。
孵育2小时后，山梨醇含量随着细胞外葡萄糖浓度的升高而增加，而肌醇含量降低。两种AR抑制剂均降低了暴露于40 mmol/L葡萄糖培养基中的中性粒细胞中山梨醇的含量。在暴露于40 mmol/L葡萄糖培养基的中性粒细胞中，肌醇含量下降70%，加入AR抑制剂后约减轻40%。高糖抑制了中性粒细胞对肌醇的摄取。AR抑制剂显著改善了肌醇摄取的减少，但未使其完全恢复正常。
我们目前的体外研究表明，葡萄糖诱导的人中性粒细胞代谢改变与易发生糖尿病并发症的组织中的改变相似，并且AR抑制剂有效地纠正了葡萄糖诱导的中性粒细胞中多元醇途径和肌醇摄取的失衡。此外，我们的研究表明，葡萄糖诱导的代谢改变可能导致中性粒细胞功能障碍，并且AR抑制剂可能能够改善这种情况。
