Prevention of spontaneous and experimentally induced diabetes in mice with zinc sulfate-enriched drinking water is associated with activation and reduction of NF-kappa B and AP-1 in islets, respectively

Exp Biol Med (Maywood). 2004 Dec;229(11):1177-85. doi: 10.1177/153537020422901113.

Abstract

Recently, we reported that zinc sulfate-enriched (25 mM) drinking water (Zn(2+)) 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)-kappa B and activator protein (AP)-1 in islets of these mice. Therefore, we studied the effect of Zn(2+) on spontaneous diabetes in female nonobese diabetic (NOD) mice and on the activity of NF-kappa B and AP-1 in islets of NOD and MLD-STZ-injected male C57BL/6 mice. We hypothesized that Zn(2+) may affect NF-kappa B, which may play a key role in immune-mediated diabetogenesis. Here we continuously administered Zn(2+) to NOD mice, to both parents and their F(1) offspring, and treated C57BL/6 male mice with MLD-STZ either alone or in addition to Zn(2+) . We assessed effects of Zn(2+) on insulitis and peri-insulitis in 8-week-old NOD mice and analyzed NF-kappa B and AP-1 activities in islets. Zn(2+) significantly prevented diabetes in female F(1) offspring and significantly reduced insulitis and peri-insulitis. Zn(2+) significantly stimulated NF-kappa B and AP-1 activation in NOD mice, in contrast, in C57BL/6 mice, Zn(2+) significantly reduced their activation by MLD-STZ. These data demonstrate that NF-kappa B may play a critical role in immune-mediated diabetes. Depending on the mode of beta-cell destruction, Zn(2+) may prevent apoptosis through activation of NF-kappa B in NOD mice or prevent inflammatory immune destruction through inhibition of NF-kappa B in MLD-STZ-treated C57BL/6 mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / prevention & control*
  • Diabetes Mellitus, Type 1 / prevention & control*
  • Drinking
  • Electrophoretic Mobility Shift Assay
  • Female
  • Islets of Langerhans / drug effects*
  • Islets of Langerhans / pathology
  • Male
  • Mice
  • Mice, Inbred NOD
  • NF-kappa B / drug effects*
  • NF-kappa B / metabolism
  • Transcription Factor AP-1 / drug effects*
  • Transcription Factor AP-1 / metabolism
  • Water
  • Zinc Sulfate / pharmacology*

Substances

  • NF-kappa B
  • Transcription Factor AP-1
  • Water
  • Zinc Sulfate