Effects of high fat, selenium‐deficient, and high‐selenium diets on diabetes biomarkers in wildtype and glutathione peroxidase‐1 null mice

Supernutritional selenium (Se, 4× RDA) in humans is associated with risk of diabetes. In mice, Se supplementation above the requirement is reported to elevate diabetes biomarkers (DB) and glutathione peroxidase‐1 (Gpx1) overexpression causes obesity and higher DB. We recently reported that high Se in mice increases transcripts associated with increased reactive oxygen (Nrf2) and altered glucose metabolism. Thus high fat, such as in US diets, might modulate impact of Se and Gpx1 on DB. Weanling (4.5 wk old) Gpx1 null (−Gpx1) and wildtype (+Gpx1) mice were fed 0, 0.1, 0.8 or 2.0 μg Se/g as selenite with low (11% cal, LF) or high fat (45% cal, HF) for 12 wk. High Se did not increase body weight whereas HF increased weight 11%. Genotype had no effect on weight in LF mice but HF increased weight in +Gpx1 mice fed 0 μg Se/g. Fasting glucose, glucose tolerance and fasting insulin were decreased by Se, and increased by HF; these effects were blunted in −Gpx1 mice, and only increased by HF in +Gpx1 mice. Unexpectedly, DB in Gpx1 heterozygote (+/−Gpx1) mice fed 0 μg Se/g were indistinguishable from −Gpx1 mice. In summary, HF, Se‐deficient and high‐Se diets had little impact on DB in −Gpx1 mice; HF with high Se had little impact in +Gpx1 mice, but HF in Se‐deficient +Gpx1 mice elevated DB but not in +/−Gpx1 mice. These results suggest that modulation of peroxide tone by diet or genotype can lead to glucose disregulation. (UW Selenium Nutrition Research)