Dietary Zinc Supplementation Inhibits NFκB Activation and Protects Against Chemically Induced Diabetes in CD1 Mice

Abstract

Zinc status in patients with Type I diabetes is significantly lower than healthy controls. Whether zinc supplementation can prevent the onset of Type I diabetes is unknown. Recent studies have suggested that the generation of reactive oxygen species (ROS) is a cause of β cell death leading to Type I diabetes. In addition, we found that activation of NFκB (a ROS-sensitive transcription factor that regulates immune responses) may be the key cellular process that bridges oxidative stress and the death of β cells. Zinc is a known antioxidant in the immune system. Therefore, this study is designed to test whether an increase in dietary zinc can prevent the onset of Type I diabetes by blocking NFκB activation in the pancreas. The results show that high zinc intake significantly reduced the severity of Type I diabetes (based on hyperglycemia, insulin level, and Islet morphology) in alloxan and streptozotocin-induced diabetic models. Zinc supplementation also inhibited NFκB activation and decreased the expression of inducible NO synthase, a downstream target gene of NFκB. It is concluded that zinc supplementation can significantly inhibit the development of Type I diabetes. The ability of zinc to modulate NFκB activation in the diabetogenic pathway may be the key mechanism for zinc's Protective effect. Inhibition of the NFκB pathway may prove to be an important criterion for choosing nutritional strategies for Type I diabetes prevention.