|HUANG, YING-CHEN - Mississippi State University|
|WU, TUNG-LUNG - Mississippi State University|
|CHENG, WEN-HSING - Mississippi State University|
Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/11/2021
Publication Date: 4/8/2021
Citation: Huang, Y., Zeng, H., Wu, T., Cheng, W. 2021. Dietary selenium requirement for the prevention of glucose intolerance and insulin resistance in middle-aged mice. Journal of Nutrition. 151:1894-1900. https://doi.org/10.1093/jn/nxab053.
Interpretive Summary: Selenium (Se) is an essential trace element for humans and animals. Studies have shown that Se is essential to prevent type 2 diabetes-like symptoms in Se-deficient mouse models. Data from these dietary models are difficult to extrapolate to clinical applications because Se deficiency in humans is rare. However, in-depth analyses suggest that 10% or 15.5 million Americans aged 40 or older are at risk for chronic disease because of Se insufficiency. In this study, we determined the nutritionally required level of dietary Se to optimize glucose homeostasis in a mouse model via different dietary Se intakes. Our experimental data provide a proof of concept that results from a mouse model fed an insufficient Se-diet are applicable to human sub-optimal Se status in the context of type-2 diabetes disease risk. The information will be useful for scientists and health-care professionals who are interested in nutrition and type-2 diabetes prevention.
Technical Abstract: Background: While serum selenium (Se) concentration in Americans is adequate (127.6 ± 17.8 ug/L), individuals with suboptimal body Se status may be symptomless and susceptible to age-related degeneration. Objective: We estimated optimized body Se status to prevent type 2 diabetes-like symptoms. Methods: Male C57BL/6J mice aged 4 mo were fed a basal modified AIN-93M Se-deficient (0.01 mg Se/kg) diet containing 24% Torula yeast or this basal diet supplemented with sodium selenate (0.03, 0.06, 0.09, and 0.12 mg Se/kg) for 18 wks (n = 6). Whole blood, serum, liver, and skeletal muscle were collected to assay for selected markers of glucose homeostasis and Se status. Data were analyzed by 1-factor ANOVA with or without time-repeated measurement. Results: Compared with the Se-adequate control diet (0.13 mg Se/kg), mice fed the basal diet showed increased (P < 0.05) body weight (5-8%; wks 14-18) and serum insulin (96%) and leptin (109%) concentrations (wk 18). Dietary Se insufficiency (0.01-0.07 mg Se/kg) induced (P < 0.05) glucose intolerance (14-79%) and insulin resistance (16-65%) in a time-dependent manner, and the onset was earlier in the former. Dietary Se insufficiency (0.01-0.10 mg Se/kg) decreased (P < 0.05) baseline AKT phosphorylation on Ser-473 and Thr-308 (22-54%) in the muscle, and glutathione peroxidase (GPX) 1 (28-84%), GPX3 (51-83%), selenoprotein P (SELENOP) (16-42%), SELENOH (39-48%), and SELENOW (16-73%) levels in the serum, liver and/or muscle. Conclusions: Adult mice fed the diets less than 0.1 mg Se/kg show impaired insulin signaling. This provides an experimental model for studying the connection between suboptimal Se status and type 2 diabetes in humans.