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.
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.
Schott-Ohly
Patricia
P
German Diabetes Center, German Diabetes Research Institute, D-40225 Düsseldorf, Germany.
Lgssiar
Abdelhakim
A
Partke
Hans-Joachim
HJ
Hassan
Mohamed
M
Friesen
Nadira
N
Gleichmann
Helga
H
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000517:prevention & control*; D003922:Diabetes Mellitus, Type 1 / Q000517:prevention & control*; D004326:Drinking; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D007515:Islets of Langerhans / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000187:drug effects* / Q000378:metabolism; D014867:Water; D019287:Zinc Sulfate / Q000494:pharmacology*
D016328:NF-kappa B; D018808:Transcription Factor AP-1; D014867:Water; D019287:Zinc Sulfate