ABSTRACT
Type I diabetes (insulin-dependent) can be produced experimentally in the laboratory with alloxan, a drug that selectively destroys pancreatic islet β-cells. Alloxan is relatively unstable, and its metabolism leads to production of free radicals (H2O2, , and HO˙), which are implicated in the pathogenesis of diabetes in laboratory animals. Zinc importance in diabetes may be reflected in its requirement in insulin storage in islet β-cells and as a component of Cu,Zn-SOD. Its function is therefore important in antioxidant activity. Clinically, diabetics have low zinc status; therefore, it is likely they possess reduced antioxidant potential. To examine the importance of zinc in protection against diabetes, alloxan has been given to transgenic mice: TGHS, a transgenic mouse line with increased Cu,Zn-SOD levels in all somatic cells, and RIPSOD, a transgenic line with increased levels of Cu,Zn-SOD only in pancreatic cells. A single dose of alloxan (50 mg/kg mouse, intravenous), given to nontransgenic control mice, raised the fasting blood glucose 150% in 5 d, relative to untreated mice. Relative to alloxan-treated controls, the same alloxan dose reduced fasting blood glucose by 50% in TGHS mice by 5 d, while fasting blood glucose levels were 75% lower in the RIPSOD strain. It is suggested that a protective effect against alloxan-induced diabetes is observed in mice with higher Cu,Zn-SOD, the RIPSOD strain exhibiting the most pronounced effect. Zinc deficiency resulted in increased susceptibility to alloxan-induced elevated fasting blood glucose level. Intraperitoneal injection of a pharmacologic dose of zinc (ZnSO4, 100 µmole/kg mouse) concurrently with alloxan, however, did not provide prophylaxis to induced diabetes.
