Zinc sulphate induces metallothionein in pancreatic islets of mice and protects against diabetes induced by multiple low doses of streptozotocin.
OBJECTIVE
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 x 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
Drinking water enriched with Zn2+ significantly up-regulated metallothionein production in pancreatic islets of mice and prevented diabetes induced with MLD-STZ.
Ohly
P
P
German Diabetes Centre, German Diabetes Research Institute, Heinrich-Heine University, Düsseldorf, Germany.
Dohle
C
C
Abel
J
J
Seissler
J
J
Gleichmann
H
H
D000818:Animals; D002478:Cells, Cultured; D003433:Crosses, Genetic; D003921:Diabetes Mellitus, Experimental / Q000517:prevention & control*; D004334:Drug Administration Schedule; D005786:Gene Expression Regulation / Q000187:drug effects*; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008668:Metallothionein / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D013311:Streptozocin / Q000008:administration & dosage; D014158:Transcription, Genetic / Q000187:drug effects; D019287:Zinc Sulfate / Q000494:pharmacology*
D012333:RNA, Messenger; D013311:Streptozocin; D019287:Zinc Sulfate; D008668:Metallothionein