The influence of aldose reductase on the oxidative burst in diabetic neutrophils.
Lucigenin-enhanced chemiluminescence was examined as an index of neutrophil superoxide production in four groups of 20 subjects: controls with/without infection and type 1 diabetics with/without infection. At 5 mM glucose there was no significant difference in chemiluminescence output between neutrophils from the four groups (P greater than 0.01). Increasing the in vitro glucose concentration from 5 to 20 mM produced an 8.75% reduction in superoxide in the combined control groups, compared with a 21.45% reduction in the diabetic subjects (P less than 0.01). With the addition of an aldose reductase inhibitor (Statil, ICI) to neutrophils from diabetic subjects, the suppression caused by an increase in glucose concentration to 20 mM was reduced to 4.5%. This value was similar to the controls (P greater than 0.01). Neutrophil aldose reductase activity, measured in 28 diabetic subjects was 0.024 +/- 0.003 U/10(8) cells (mean +/- SE). There was a significant correlation between aldose reductase activity and superoxide suppression (P less than 0.01, r = 0.64). These results suggest that aldose reductase is responsible for reduced superoxide production in diabetic patients and the addition of an aldose reductase inhibitor to the diabetic neutrophil restores superoxide output to control values.
Tebbs
S E
SE
Department of Medicine and Pharmacology, Royal Hallamshire Hospital, Sheffield, U.K.
Lumbwe
C M
CM
Tesfaye
S
S
Gonzalez
A M
AM
Wilson
R M
RM
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors / Q000097:blood*; D001786:Blood Glucose / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications; D005260:Female; D016523:Foot Ulcer / Q000097:blood; D005947:Glucose / Q000494:pharmacology; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010793:Phthalazines / Q000494:pharmacology*; D012016:Reference Values; D016897:Respiratory Burst / Q000187:drug effects*; D012141:Respiratory Tract Infections / Q000097:blood* / Q000150:complications; D013481:Superoxides / Q000097:blood
D000449:Aldehyde Reductase; D001786:Blood Glucose; D005947:Glucose; D006442:Glycated Hemoglobin; D010793:Phthalazines; D013481:Superoxides; C042829:ponalrestat