Selenium, an Ambivalent Factor in Diabetes? Established Facts, Recent Findings and Perspectives

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It is widely known that selenium develops its biological activity via an active selenocysteine residue in the catalytically active centre of functional selenoproteins. By its function in glutathione peroxidases and thioredoxin reductases selenium contributes to a remarkable extent to the maintenance of the cellular antioxidative balance when taken up at the recommended dietary level (animals: 0.1 - 0.3 μg/kg diet, humans: 50 - 150 µg Se daily). In recent years an interesting physiological aspect has been found for selenate (selenium oxidation state +VI). High doses of selenate displayed antidiabetic properties when applied to diabetic animals or added to the media of tissue cultures. Thus selenate treatment could be shown to normalise hyperglycaemia as well as changed activities of glycolytic and gluconeogenic marker enzymes. Mechanistically an increased phosphorylation of single proteins of the insulin signalling cascade could be attributed to the insulinomimetic action of selenate. The examination of the antidiabetic features of selenate in type II diabetic animals revealed that the increase in phosphorylation is presumably based on the inhibition of protein tyrosine phosphatases, which act as negative regulators of insulin signalling. In contrast to the antidiabetic features of high selenate doses, selenite administration to diabetic animals showed no effect on diabetes. In a recent study it could even be demonstrated that the overexpression of glutathione peroxidase 1 (the best characterized selenoprotein) in healthy mice led to an increase in insulin resistance and obesity. These results could partially be confirmed by the data of our most recent investigation in which a high expression and activity of glutathione peroxidase, obtained by feeding selenium at the nutritionally recommended level and at a moderately supranutritive level corresponded to an up-regulated expression of proteins whose expression is increased in insulin resistant type 2 diabetes. From studies on the role of selenium in diabetes carried out so far it can be concluded that selenium plays an ambivalent role with regard to diabetes depending on the compound and on the applied concentration. Thus only high doses of selenate evolve antidiabetic properties. Investigations into an even negative influence of moderate supranutritive doses of selenium on diabetes and the molecular events linked to this are necessary. The review summarizes the information currently available on the ambivalent role of selenium in diabetes which seems to depend on the chemical form and the applied concentration. Established facts, recent findings of our own studies using microarray analysis and RT-PCR and perspectives of the role of selenium in diabetes are presented and discussed against the background of selenium metabolism. Keywords: Selenium, selenate, selenite, antidiabetic effects and insulin resistance