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• W2079236712 abstract "Background: Glucose is the main substrate for the generationof NADPH, the cofactor of the oxidative burst enzyme NADPH-oxidase of bloodneutrophils. Changes in blood glucose are thus expected to modify thegeneration of reactive oxygen species (ROS). The new blood ROS generation assay(BRGA) quantifies ROS changes induced by blood glucose concentrations as theyare found in diabetes mellitus. Material and Methods: Citrated or EDTA blood of 6 healthy donorswere analyzed in the BRGA: 10 μl sample in black polystyrene F-microwells(Brand 781608) were incubated intriplicate with 125 μl Hanks’ balancedsalt solution, 40 μl 0 - 200 mM glucose in 0.9% NaCl (final added conc.: 0 - 41mM; final basal glucose conc.: about4 mM),10 μl5 mMluminol,and 10 μl zymosan A (final conc.: 1.9 μg/ml) in 0.9% NaCl. The plates weremeasured within 0 - 250 min (37℃) in a photons-multiplyer microtiter plateluminometer (LUmo) with an integration time of 1 s. Results: Up to about 30 min reaction time themean ROS generation was 50% inhibited by about1 mMadded glucose (= approx. IC50). At ≥80 min reaction time (possiblynecessary for full phosphorylation of glucose to glucose-6-phosphate (G6P), thesubstrate metabolized by G6P-dehydrogenase to generate NADPH, the cofactor ofthe NADPH-oxidase) the mean ROS generation approximately doubled at about1 mMadded glucose (= approx. SC200) in citrated blood. Discussion: Elevated glucose concentrations not only increase systemicthrombin generation, they can also diminish cellular fibrinolysis and increasesystemic inflammation, resulting in a chronic pro-thrombotic state. Thefascinating importance of NADPH-oxidases not only in phagocytes but also in thebeta cells of pancreas points towards a new pathogenesis explication ofdiabetes mellitus type 1: whatever stimulus (e.g. a pancreas-tropic virus)could activate the beta cell’s autodestructive NADPH-oxidase." @default.
• W2079236712 created "2016-06-24" @default.
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• W2079236712 date "2013-01-01" @default.
• W2079236712 modified "2023-09-30" @default.
• W2079236712 title "Glucose initially inhibits and later stimulates blood ROS generation" @default.
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• W2079236712 doi "https://doi.org/10.4236/jdm.2013.31003" @default.
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