MT does not protect endocrine cell damage induced by alloxan in pancreas of mice

Abstract

Metallothionein (MT) has been proposed to have various functions, such as detoxification of heavy metals, storage of essential metals, and scavenging of free radicals. Induction of MT by zinc is reported to reduce both endocrine and exocrine damages of the pancreas induced by chemicals. However, the damage is not inhibited completely. The first question is that an essential concentration zone of zinc is too narrow to apply to organs, especially to the pancreas. It is, of course, that zinc is an essential metal. Zinc acts as an essential cofactor for many metalloenzymes with various biological functions. Zinc, itself, has antioxidant action, and prevents the production of hydroxyl and superoxide radicals. Zinc is needed for storage of insulin in the pancreas, and zinc contents in the plasma and urine are altered in diabetes. However, excess zinc may cause toxic effect in pancreas, as we observed congestion of the pancreas after zinc administration. The other question is that no MT was detected immunohistochemically in the endocrine cells after the administration of zinc. Andrews et al. [1] reported that mRNA of MT was detected in both the exocrine and endocrine cells. Ohly and Gleichmann [2] also observed MT induction in the isolated islets of pancreas by zinc and streptozotocin. MT has a strong radical scavenging action, and alloxan is used for an experimental model of type-1 diabetes. Alloxan generates superoxide radicals, and causes hyperglycemia and hypoinsulinemia. As the destruction of 13-cell is mediated by superoxide and nitric oxide radicals, MT may have a protective role in the endocrine cells. However, we previously observed immunohistochemically that MT was located in the exocrine cells, but not in the endocrine cells after zinc injection to mice. In addition, Apostolova et al. [3] reported that the pretreatment of zinc inhibited the streptozotocin-induced diabetes in MT-null mice. Is MT induced in the endocrine cells by zinc? The object of this study was to elucidate the induction of MT in endocrine cells of pancreas as well as the possible role of MT in preventing oxidative damage induced by alloxan.KeywordsEndocrine CellPlasma Glucose LevelControl Vehicle GroupExocrine CellExcess ZincThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.