Metabolic alterations in the human erythrocyte produced by increases in glucose concentration. The role of the polyol pathway.

Metabolic alterations in the human erythrocyte produced by increases in glucose concentration. The role of the polyol pathway.
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DOI:
10.1172/jci106704
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发表时间:
1971-10
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
S. Travis;A. D. Morrison;R. Clements;A. Winegrad;F. Oski
S. Travis;A. D. Morrison;R. Clements;A. Winegrad;F. Oski
中科院分区:
其他
文献类型:
--
作者:
S. Travis;A. D. Morrison;R. Clements;A. Winegrad;F. Oski

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与用5 mM葡萄糖孵育的样品相比,在含有50 mM葡萄糖的培养基中孵育的人红细胞具有增加的细胞内山梨糖醇和果糖浓度。增加培养基葡萄糖浓度并不显著改变总葡萄糖消耗或乳酸产生。然而,细胞内乳酸:丙酮酸的比例上升,果糖二磷酸和磷酸丙糖的浓度增加,2,3-二磷酸甘油酸浓度下降。葡萄糖-1-(14)C产生的[(14)C]O(2)也随培养基葡萄糖浓度的增加而增加。这些变化被认为反映了由多元醇途径的活性增加引起的二磷酸吡啶核苷酸/二磷酸吡啶核苷酸的还原形式(NAD/NADH)和烟酰胺-腺嘌呤二核苷酸磷酸/烟酰胺-腺嘌呤二核苷酸磷酸的还原形式(NADP/NADPH)对的氧化还原状态的变化。向孵育培养基中添加丙酮酸盐可防止这些变化。这些研究表明,增加红细胞的正常底物,葡萄糖,可以产生红细胞代谢的变化。
Human erythrocytes incubated in medium containing 50 mM glucose have increased intracellular sorbitol and fructose concentrations as compared with samples incubated with 5 mM glucose. Increased medium glucose concentration did not significantly alter total glucose consumption or lactate production. However, the intracellular lactate:pyruvate ratio rose, the concentrations of fructose diphosphate, and triose phosphates increased, and the 2,3-diphosphoglycerate concentration fell. [(14)C]O(2) production from glucose-1-(14)C also increased with increased medium glucose concentration. These changes are believed to reflect changes in the redox states of the diphosphopyridine nucleotide/reduced form of diphosphopyridine nucleotide (NAD/NADH) and nicotinamide-adenine dinucleotide phosphate/reduced form of nicotinamide-adenine dinucleotide phosphate (NADP/NADPH) couples resulting from increased activity of the polyol pathway. Addition of pyruvate to the incubation media prevented these changes. These studies illustrate that an increase in the red cell's normal substrate, glucose, can produce changes in red cell metabolism.