caa a22 4500 47577261X CHVBK 20180406123621.0 cr unu---uuuuu 170329e20000801xx s 000 0 eng 10.1007/s001250050009 doi (NATIONALLICENCE)springer-10.1007/s001250050009 Zinc sulphate induces metallothionein in pancreatic islets of mice and protects against diabetes induced by multiple low doses of streptozotocin [Elektronische Daten] [P. Ohly, C. Dohle, J. Abel, J. Seissler, H. Gleichmann] Aims/hypothesis. Diabetes is induced by multiple low doses of streptozotocin (MLD-STZ) in male mice of susceptible strains. In this model beta-cell injury and T-cell-mediated inflammatory reactions are induced. Probably, reactive oxygen species (ROS) participate in the destruction of beta cells. The effects of ROS can be counterbalanced by several antioxidant systems. One of these is metallothionein (MT), cytosolic proteins that are induced by zinc ions (Zn2+) and scavenge hydroxyl radicals (·OH). The effect of Zn2+ on MLD-STZ-diabetes was studied. Methods. We gave C57BL/6 and (C57BL/6 × SJL)F1 hybrid mice either MLD-STZ or in addition Zn2+-enriched drinking water. We analysed metallothionein ex vivo in pancreatic islets for protein and mRNA concentration for the isoforms 1 and 2. Pancreatic sections were examined by immunohistochemistry for metallothionein and histologically for insulitis. Results. In both strains, Zn2+-enriched drinking water significantly up-regulated metallothionein and prevented MLD-STZ-diabetes and loss of beta-cell function. In the F1 hybrid mice a variant of MLD-STZ-diabetes was observed. These mice developed hyperglycaemia 10 weeks after the first injection of STZ (in contrast to 2 weeks observed in other mouse strains) and pronounced insulitis. The mRNA of the metallothionein isoforms 1 and 2 were constitutively expressed and slightly up-regulated by Zn2+-enriched drinking water. All islets cells stained for metallothionein. Conclusions/interpretations. Drinking water enriched with Zn2+ significantly up-regulated metallothionein production in pancreatic islets of mice and prevented diabetes induced with MLD-STZ. [Diabetologia (2000) 43: 1020-1030] Springer-Verlag Berlin Heidelberg, 2000 Keywords Streptozotocin nationallicence metallothionein nationallicence zinc sulphate nationallicence diabetes nationallicence beta cells nationallicence Ohly P. German Diabetes Centre, German Diabetes Research Institute, Heinrich-Heine University, Düsseldorf, Germany, DE aut Dohle C. German Diabetes Centre, German Diabetes Research Institute, Heinrich-Heine University, Düsseldorf, Germany, DE aut Abel J. Division of Toxicology, Medical Institute of Environmental Hygiene, Heinrich-Heine University, Düsseldorf, Germany, DE aut Seissler J. German Diabetes Centre, German Diabetes Research Institute, Heinrich-Heine University, Düsseldorf, Germany, DE aut Gleichmann H. German Diabetes Centre, German Diabetes Research Institute, Heinrich-Heine University, Düsseldorf, Germany, DE aut https://doi.org/10.1007/s001250050009 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001250050009 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ohly P. German Diabetes Centre, German Diabetes Research Institute, Heinrich-Heine University, Düsseldorf, Germany, DE aut NATIONALLICENCE 700 1- Dohle C. German Diabetes Centre, German Diabetes Research Institute, Heinrich-Heine University, Düsseldorf, Germany, DE aut NATIONALLICENCE 700 1- Abel J. Division of Toxicology, Medical Institute of Environmental Hygiene, Heinrich-Heine University, Düsseldorf, Germany, DE aut NATIONALLICENCE 700 1- Seissler J. German Diabetes Centre, German Diabetes Research Institute, Heinrich-Heine University, Düsseldorf, Germany, DE aut NATIONALLICENCE 700 1- Gleichmann H. German Diabetes Centre, German Diabetes Research Institute, Heinrich-Heine University, Düsseldorf, Germany, DE aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer