Oxidative/nitrosative stresses trigger type I diabetes: preventable in streptozotocin rats and detectable in human disease

Ann N Y Acad Sci. 2010 Aug:1203:138-45. doi: 10.1111/j.1749-6632.2010.05563.x.

Abstract

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.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Experimental / prevention & control*
  • Diabetes Mellitus, Type 1 / diagnosis
  • Diabetes Mellitus, Type 1 / etiology*
  • Diabetes Mellitus, Type 1 / metabolism*
  • Diabetes Mellitus, Type 1 / prevention & control
  • Humans
  • Oxidation-Reduction
  • Oxidative Stress / physiology*
  • Rats
  • Reactive Nitrogen Species / metabolism*
  • Reactive Oxygen Species / metabolism
  • Species Specificity

Substances

  • Reactive Nitrogen Species
  • Reactive Oxygen Species