Selenium and diabetes--evidence from animal studies.

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.