Oxidative/nitrosative stresses trigger type I diabetes: preventable in streptozotocin rats and detectable in human disease.
Recently we demonstrated that streptozotocin (STZ) diabetes (type I) in rats is preventable using a simultaneous equimolar injection of carboxy-PTIO (c-PTIO). Both changes in blood sugar and cataracts are prevented. This apparently occurs because the nitric oxide (NO) (from STZ) generated in the beta cells is oxidized to nitrite by c-PTIO preventing diabetes. STZ generates NO producing a NO-based toxin. The toxin damages DNA by nicking and activates poly-ADP-ribose causing necrosis and triggering inflammation. Is there evidence that O/N stress occurs in early human type I diabetes? We studied 40 children with or without early type I diabetes and observed that urate is decreased 25% in all these diabetic children each over the age of 3 years. Urate is a major portion of blood-antioxidant load. Surely this decrease in urate indicates ongoing O/N stress. Does O/N stress initiate disease? STZ studies in rats indicates that this is correct.
Van Dyke
Knox
K
Department of Biochemistry and Molecular Biology/Physiology-Pharmacology, West Virginia University Medical School, West Virginia, USA. kvandyke@hsc.wvu.edu
Jabbour
Nabil
N
Hoeldtke
Robert
R
Van Dyke
Chris
C
Van Dyke
Mark
M
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000517:prevention & control*; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism* / Q000517:prevention & control; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013045:Species Specificity
D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species