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  • Title: Effects of glucose and SNK-860, an aldose reductase inhibitor, on the polyol pathway and chemiluminescence response of human neutrophils in vitro.
    Author: Kawamura T, Suzuki K, Matsumae H, Sano T, Sakamoto N, Hotta N.
    Journal: Diabet Med; 1995 May; 12(5):392-6. PubMed ID: 7648800.
    Abstract:
    An in vitro incubation study was conducted to investigate whether increased activity of the polyol pathway in human neutrophils under diabetic conditions resulted in a decrease of superoxide anion produced by NADPH oxidase on the membrane of neutrophils. Lucigenin-enhanced chemiluminescence (CL) to phorbol myristate acetate as respiratory burst and sorbitol levels in neutrophils after incubation with glucose and an aldose reductase (AR) inhibitor, SNK-860 (SNK) were measured. Sorbitol levels increased from 0.210 +/- 0.029 nmol 10(7) cells-1 in 5 mmol l-1 glucose to 0.446 +/- 0.036 nmol 10(7) cells-1 in 40 mmol l-1 glucose, while CL decreased from 0.542 +/- 0.034 cpm cell-1 in 5 mmol l-1 glucose to 0.430 +/- 0.018 cpm cell-1 in 40 mmol l-1 glucose. The addition of 10 mumol l-1 SNK normalized the increased sorbitol levels in neutrophils exposed to 40 mmol l-1 glucose and improved, but did not normalize, the decrease in CL induced by 40 mmol l-1 glucose (p < 0.001). Galactose (40 mmol l-1) also reduced CL, which was improved by the addition of SNK (p < 0.01). These results suggest that impaired respiratory burst induced by high-glucose concentrations is caused by competition for NADPH resulting from increased polyol pathway activity and/or glycation and that an AR inhibitor may be capable in part of preventing increased susceptibility to infection in diabetic patients.
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