High selenium intake and increased diabetes risk: experimental evidence for interplay between selenium and carbohydrate metabolism |
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Authors: | Steinbrenner Holger Speckmann Bodo Pinto Antonio Sies Helmut |
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Institution: | 1.Institute for Biochemistry and Molecular Biology I, Medical Factory, Heinrich-Heine-Universität, Düsseldorf, Universitätsstrasse 1, Geb. 22.03, D-40225 Düsseldorf, Germany;2.Institut für Umweltmedizinische Forschung (IUF) an der Heinrich-Heine-Universität, Auf’m Hennekamp 50, D-40225 Düsseldorf, Germany;3.College of Science, King Saud University, Riyadh, Saudi Arabia |
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Abstract: | The essential trace element selenium has long been considered to exhibit anti-diabetic and insulin-mimetic properties, but recent epidemiological studies indicated supranutritional selenium intake and high plasma selenium levels as possible risk factors for development of type 2 diabetes, pointing to adverse effects of selenium on carbohydrate metabolism in humans. However, increased plasma selenium levels might be both a consequence and a cause of diabetes. We summarize current evidence for an interference of selenium compounds with insulin-regulated molecular pathways, most notably the phosphoinositide-3-kinase/protein kinase B signaling cascade, which may underlie some of the pro- and anti-diabetic actions of selenium. Furthermore, we discuss reports of hyperinsulinemia, hyperglycemia and insulin resistance in mice overexpressing the selenoenzyme glutathione peroxidase 1. The peroxisomal proliferator-activated receptor gamma coactivator 1α represents a key regulator for biosynthesis of the physiological selenium transporter, selenoprotein P, as well as for hepatic gluconeogenesis. As proliferator-activated receptor gamma coactivator 1α has been shown to be up-regulated in livers of diabetic animals and to promote insulin resistance, we hypothesize that dysregulated pathways in carbohydrate metabolism and a disturbance of selenium homeostasis are linked via proliferator-activated receptor gamma coactivator 1α. |
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Keywords: | selenoprotein glutathione peroxidase hyperglycemia insulin PGC-1α Akt |
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