Dietary zinc supplementation inhibits NFkappaB activation and protects against chemically induced diabetes in CD1 mice.
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 beta cell death leading to Type I diabetes. In addition, we found that activation of NFkappaB (a ROS-sensitive transcription factor that regulates immune responses) may be the key cellular process that bridges oxidative stress and the death of beta 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 NFkappaB 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 NFkappaB activation and decreased the expression of inducible NO synthase, a downstream target gene of NFkappaB. It is concluded that zinc supplementation can significantly inhibit the development of Type I diabetes. The ability of zinc to modulate NFkappaB activation in the diabetogenic pathway may be the key mechanism for zinc's protective effect. Inhibition of the NFkappaB pathway may prove to be an important criterion for choosing nutritional strategies for Type I diabetes prevention.
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Department of Human Nutrition, The Ohio State University, Columbus 43210, USA.
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Tsai
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Lai
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Bray
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D000496:Alloxan; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000178:diet therapy*; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000178:diet therapy*; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000473:pathology; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000302:isolation & purification; D052247:Nitric Oxide Synthase Type II; D013311:Streptozocin; D014886:Weaning; D015032:Zinc / Q000627:therapeutic use*
D001786:Blood Glucose; D007328:Insulin; D016328:NF-kappa B; D013311:Streptozocin; D000496:Alloxan; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D015032:Zinc