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Review
. 2013 Dec:65:1548-1556.
doi: 10.1016/j.freeradbiomed.2013.07.012. Epub 2013 Jul 16.

Selenium and diabetes--evidence from animal studies

Jun Zhou  1 , Kaixun Huang  1 , Xin Gen Lei  2
Affiliations
Review

Selenium and diabetes--evidence from animal studies

Jun Zhou et al. Free Radic Biol Med. 2013 Dec.

Abstract

Whereas selenium was found to act as an insulin mimic and to be antidiabetic in earlier studies, recent animal experiments and human trials have shown an unexpected risk of prolonged high Se intake in potentiating insulin resistance and type 2 diabetes. Elevating dietary Se intake (0.4 to 3.0mg/kg of diet) above the nutrient requirements, similar to overproduction of selenoproteins, led to insulin resistance and/or diabetes-like phenotypes in mice, rats, and pigs. Although its diabetogenic mechanism remains unclear, high Se intake elevated activity or production of selenoproteins including GPx1, MsrB1, SelS, and SelP. This upregulation diminished intracellular reactive oxygen species and then dysregulated key regulators of β cells and insulin synthesis and secretion, leading to chronic hyperinsulinemia. Overscavenging intracellular H2O2 also attenuated oxidative inhibition of protein tyrosine phosphatases and suppressed insulin signaling. High Se intake might affect expression and/or function of key regulators of glycolysis, gluconeogenesis, and lipogenesis. Future research is needed to find out if certain forms of Se metabolites in addition to selenoproteins and if mechanisms other than intracellular redox control mediate the diabetogenic effects of high Se intake. Furthermore, a potential interactive role of high Se intake in the interphase of carcinogenesis and diabetogenesis should be explored to make optimal use of Se in human nutrition and health.

Keywords: AKT; AMPK; BD; Diabetes; FOX; Free radicals; GPx1; GSIS; H3; H4; HbA(1c); IR; IRS; Insr; Insulin; KO; MsrB1; NPC; Nutritional Prevention of Cancer; OE; PDX1; PGC-1α; PI3-K; PTEN; PTP1b; PTPase; ROS; Reactive oxygen species; SELECT; SOD; SREBP-1c; Scly; Sel; Selenium; Selenium and Vitamin E Cancer Prevention Trial; Selenoprotein; TrxR; UCP2; WT; adenosine monophosphate-activated protein kinase; basal diet; forkhead box; glucose-stimulated insulin secretion; glutathione peroxidase 1; hemoglobin A(1c); histone 3; histone 4; insulin receptor; insulin receptor substrate; knockout; methionine-R-sulfoxide reductase 1; overexpressing; pancreatic duodenal homeobox 1; peroxisomal proliferator-activated receptor-γ coactivator 1α; phosphatase with tensin homology; phosphatidylinositol 3-kinase; phosphotyrosine phosphatase; protein kinase B; protein tyrosine phosphatase 1b; reactive oxygen species; selenocysteine lyase; selenoprotein; sterol regulatory element-binding protein-1c; superoxide dismutase; thioredoxin reductase; uncoupling protein 2; wild type.

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Conflict of interest statement

Conflict of interest statement

The authors declare that there are no conflicts of interest.

Figures

Figure 1
Figure 1
Scheme of potential regulatory pathways and mechanisms for the diabetogenic potential of high Se intake. ↑, Activation or increase; ↓, inhibition or decrease; Akt, protein kinase B; FOXO1, forkhead box O1; GPx1, glutathione peroxidase-1; GSIS, glucose-stimulated insulin secretion; H2O2, hydrogen peroxide; IR, insulin receptor; P, phosphorylation; PY, tyrosine phosphorylation; PTEN, phosphatase with tensin homology; PTP1b, protein tyrosine phosphatase 1b; SREBP1c, sterol regulatory element binding protein-1c; TC, total cholesterol; TG, triglyceride.
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