Related Experiment Videos
Involvement of O2 radicals in 'autoimmune' diabetes
I N Nomikos1, Y Wang, K J Lafferty
1Barbara Davis Center for Childhood Diabetes, Department of Microbiology/Immunology, Pediatrics, University of Colorado Health Sciences Center, Denver 80262.
Abstract:
Spontaneous diabetes in the non-obese diabetic (NOD) mice is a CD4 T cell-dependent process. We have suggested that specific beta cell destruction results from free radical production at the site of islet inflammation; oxygen radicals are produced by activated inflammatory cells. We reported here that in vivo treatment of spontaneously diabetic NOD mice with the enzyme superoxide dismutase (2000 U for seven injections) and catalase (40,000 U for seven injections) protects islet tissue from disease recurrence following transplantation into spontaneously diabetic mice. Similar results were obtained when animals were treated with either enzyme alone. This effect was dose-dependent and little protection was observed when the dose of enzyme was reduced four-fold. These results indicate that oxygen metabolites, specially superoxide and hydrogen peroxide, are directly involved in the pathogenesis of immunology mediated diabetes.
Insights
Superoxide dismutase and catalase enzymes protect islet tissue in non-obese diabetic mice. These findings suggest oxygen metabolites are key in immune-mediated diabetes pathogenesis.
Area of Science:
- Immunology
- Endocrinology
- Diabetes Research
Background:
- Spontaneous diabetes in non-obese diabetic (NOD) mice is a CD4 T cell-dependent autoimmune disease.
- Beta cell destruction is linked to free radical production by inflammatory cells at the islet inflammation site.
Purpose of the Study:
- To investigate the role of oxygen metabolites in immune-mediated diabetes.
- To determine if antioxidant enzymes can protect islet tissue from recurrence after transplantation.
Main Methods:
- In vivo treatment of spontaneously diabetic NOD mice with superoxide dismutase and catalase.
- Assessment of islet tissue protection following transplantation into diabetic recipients.
- Dose-dependency analysis of enzyme treatment efficacy.
Main Results:
- In vivo treatment with superoxide dismutase and catalase protected islet tissue from recurrence.
- Similar protective effects were observed when enzymes were administered individually.
- The protective effect was dose-dependent, with reduced efficacy at lower doses.
Conclusions:
- Oxygen metabolites, specifically superoxide and hydrogen peroxide, are directly implicated in the pathogenesis of immune-mediated diabetes.
- Antioxidant enzymes demonstrate potential in preventing islet tissue destruction in autoimmune diabetes models.