Prevention of Spontaneous and Experimentally Induced Diabetes in Mice With Zinc Sulfate-Enriched Drinking Water Is Associated with Activation and Reduction of NF-κB and AP-1 in Islets, Respectively

Recently, we reported that zinc sulfate-enriched (25 mM) drinking water (Zn2+) protected male C57BL/6 mice from diabetes induced by multiple low doses of streptozotocin (MLD-STZ) and that MLD-STZ activates the transcription factors nuclear factor (NF)-κB and activator protein (AP)-1 in islets of these mice. Therefore, we studied the effect of Zn2+ on spontaneous diabetes in female nonobese diabetic (NOD) mice and on the activity of NF-κB and AP-1 in islets of NOD and MLD-STZ–injected male C57BL/6 mice. We hypothesized that Zn2+ may affect NF-κB, which may play a key role in immune-mediated diabetogenesis. Here we continuously administered Zn2+ to NOD mice, to both parents and their F1 offspring, and treated C57BL/6 male mice with MLD-STZ either alone or in addition to Zn2+. We assessed effects of Zn2+ on insulitis and peri-insulitis in 8-week-old NOD mice and analyzed NF-κB and AP-1 activities in islets. Zn2+ significantly prevented diabetes in female F1 offspring and significantly reduced insulitis and p...