Minimum Dietary Selenium Requirement to Prevent Type 2 Diabetes in Mice

Abstract

Abstract Objectives Classic selenium (Se) deficiency syndromes are rare in the United States, but individuals with sub-optimal body Se status free of symptoms may be prone to certain chronic diseases such as diabetes if the condition is sustained. In-depth analyses of the National Health and Nutrition Examination Survey estimate that mortality rate is increased when serum Se is < 105.8 μg/L, suggesting that Se status in 10% or 15.5 million Americans aged 40 or older might be sub-optimal. Nonetheless, previous mouse studies show that both dietary selenium deficiency and in excess can promote type 2 diabetes. In this study, we determined the minimally required intake of dietary Se for prevention of type 2 diabetes-like phenotype in mice. Methods Male C57BL/6 J mice at 4 months of age were fed a modified AIN-93 M Se(-) diet containing 24% Torula yeast or the basal diet (0.0072 Se/kg) added with sodium selenate (0.03, 0.06, 0.09, and 0.12 mg Se/kg) for 4 months (n = 6 per group). Glucose tolerance and insulin sensitivity were determined at 5, 6 and 8 months of age. Blood, liver, pancreas and muscle were collected at 8 months of age for biochemical analysis. Results Compared to the Se-adequate diet added with 0.12 mg Se/kg, mice on the Se(-) diet showed increased (P < 0.05) body weight at 7–8 months of age and mice on the Se(-) diet added with 0, 0.03 or 0.06 but not 0.09 mg Se/kg displayed glucose intolerance and insulin resistance in a temporal manner. Results of Western analyses showed that levels of serum glutathione peroxidase 3 and muscle AKT phosphorylation on Ser-473 and Thr-308 were decreased (P < 0.05) in mice on the diets added with 0–0.09 mg Se/kg. Conclusions Collectively, we show that mature mice on Se-insufficient diet at levels lower than 0.09 mg Se/kg for 4 months display sub-optimal body Se status and develop type 2 diabetes-like phenotype. Funding Sources NIH.