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Free Radic Biol Med. 2013 Dec;65:1538-1547. doi: 10.1016/j.freeradbiomed.2013.07.016. Epub 2013 Jul 18.

Interference of selenium and selenoproteins with the insulin-regulated carbohydrate and lipid metabolism.

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Institute for Biochemistry and Molecular Biology I, Heinrich-Heine-Universität, Düsseldorf, Germany. Electronic address:


An assumed link between supranutritional intake of the micronutrient selenium (Se) and type 2 diabetes mellitus is discussed controversially. Se concentrations in the habitual diet and in dietary supplements are probably not sufficient to induce overt diabetes in healthy individuals. On the other hand, high plasma Se and selenoprotein P (Sepp1) levels have been found to be associated with biomarkers of an impaired carbohydrate and lipid homeostasis in humans. Moreover, abundant expression of antioxidant selenoproteins due to dietary Se oversupply resulted in hyperinsulinemia and decreased insulin sensitivity in animal models. This review discusses findings from animal and cell culture studies in search of molecular mechanisms underlying an interference of Se and selenproteins such as the Se transport and supply protein Sepp1 and the hydrogen peroxide-reducing selenoenzyme glutathione peroxidase 1 (GPx1) with insulin-controlled metabolic pathways. A probable rationale derives from the positive and negative regulation of both glucose-induced insulin secretion and insulin-induced signaling by hydrogen peroxide. Se status and GPx1 expression have been reported to affect the activity of insulin-antagonistic phosphatases that are regulated by hydrogen peroxide-mediated reversible oxidation of catalytic cysteine residues. GPx1 and/or Sepp1 inhibited phosphorylation (activation) of key mediators in energy metabolism such as protein kinase B (Akt) and AMP-activated protein kinase (AMPK) in liver and/or skeletal muscle. Conversely, a dys-regulated carbohydrate metabolism in diabetes might affect plasma Se and Sepp1 levels, as the hepatic biosynthesis of Sepp1 is suppressed by insulin and stimulated under hyperglycemic conditions.


AMP-activated protein kinase; AMPK; Akt; ApoER2; Diabetes; ERK; FoxO; Free radicals; GLUT; GPx; GSIS; Glutathione peroxidase; HNF-4α; Hydrogen peroxide; IR; IRS; Insulin resistance; MAPK; MsrB; NADPH oxidase; Nox; PGC-1α; PKC; PTEN; PTP-1B; ROS; SOD; SREBP1c; Se; Selenoprotein P; Sepp1; T2DM; TrxR; UCP-2; apolipoprotein E receptor 2; extracellular signal-regulated kinase; forkhead box class O; glucose transporter; glucose-stimulated insulin secretion; glutathione peroxidase; hepatocyte nuclear factor 4α; insulin receptor; insulin receptor substrate; methionine sulfoxide reductase B; mitogen-activated protein kinase; peroxisomal proliferator-activated receptor gamma coactivator 1α; phosphatase and tensin homolog; protein kinase B; protein kinase C; protein tyrosine phosphatase 1B; reactive oxygen species; selenium; selenoprotein P; sterol regulatory element binding protein 1c; superoxide dismutase; thioredoxin reductase; type 2 diabetes mellitus; uncoupling protein 2

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