Selenium (Se) is an essential micronutrient in mammals tiiat exerts its function in the context of selenocysteine-containing proteins. The group of selenoproteins is represented by more than 50 protein families;however, they all appear to contribute to antioxidant and redox regulation by being selenoprotein forms of thiol oxidoreductases. The human selenoproteome consists of 25 selenoproteins which are involved in protection against oxidative stress, signal transduction, and the folding, modification, and regulation of proteins. Selenoprotein expression depends on dietary Se content. Intriguingly, recent clinical trials suggest that Se over-nutrition may significantly raise the risk of type 2 diabetes development. Subsequent studies involving mouse models demonstrated that low and high Se intake are both associated with the type 2 diabetes-like phenotype;however, specific mechanisms of this phenomenon have not been investigated. Different regions of the world are characterized by significant variations in Se content in soil and the associated variation in dietary Se content. Many regions of the United States are Se-rich, and the United States population is characterized by high levels of Se in plasma and, therefore, may have increased risk of diabetes development. In addition, the use of Se-rich dietary supplements in such areas may have a negative impact on health and increase the incidence of diabetes. The goal of this project is to investigate the roles of Se and selenoproteins in redox regulation of glucose homeostasis. The central hypothesis is that Se regulates selenoprotein synthesis which, in turn, alters redox homeostasis and influences the insulin signaling pathways. Specifically, Dr. Fomenko will define the effects of Se supplementation on redox-dependent insulin signaling. This work will be guided by two specific aims: (1) identify mechanisms underlying Se-dependent type 2 diabetes development;and (2) assess the contribution of selenoproteins to H2O2 signaling and associated control of glucose homeostasis.
These aims will be addressed using a combination of biochemical and cell biology studies and animal models. The proposed study fits with the mission of the Nebraska Center for the Prevention of Obesity Diseases through Dietary Molecules (NPOD) and will help identify mechanisms of Se micronutrient-associated diabetes development. NPOD support, facilities, and mentoring will allow Dr. Fomenko to advance this project toward an independent R01 award and achieve his long-term research goals in Se biology.

Public Health Relevance

Contradictory effects observed in previous clinical trials on the role of Se in cancer prevention and reported diabetes-related side effects suggest an optimal level of dietary Se may be redefined to provide health benefits while lowering the risk of diabetes development. This project aims to provide the molecular basis for this hypothesis, representing the first attempt to explain regulation of glucose homeostasis by Se and describe mechanisms of the redox control of insulin signaling by selenoproteins.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Exploratory Grants (P20)
Project #
Application #
Study Section
Special Emphasis Panel (ZGM1-TWD-C (C1))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Nebraska Lincoln
United States
Zip Code
Kim, Jiyoung; Okla, Meshail; Erickson, Anjeza et al. (2016) Eicosapentaenoic Acid Potentiates Brown Thermogenesis through FFAR4-dependent Up-regulation of miR-30b and miR-378. J Biol Chem 291:20551-62
Wang, Hai; Zhao, Miaoyun; Sud, Neetu et al. (2016) Glucagon regulates hepatic lipid metabolism via cAMP and Insig-2 signaling: implication for the pathogenesis of hypertriglyceridemia and hepatic steatosis. Sci Rep 6:32246
Lu, Sizhao; Natarajan, Sathish Kumar; Mott, Justin L et al. (2016) Ceramide Induces Human Hepcidin Gene Transcription through JAK/STAT3 Pathway. PLoS One 11:e0147474
Farris, Eric; Brown, Deborah M; Ramer-Tait, Amanda E et al. (2016) Micro- and nanoparticulates for DNA vaccine delivery. Exp Biol Med (Maywood) 241:919-29
Krumbeck, Janina A; Maldonado-Gomez, Maria X; Ramer-Tait, Amanda E et al. (2016) Prebiotics and synbiotics: dietary strategies for improving gut health. Curr Opin Gastroenterol 32:110-9
Cordonier, Elizabeth L; Jarecke, Sarah K; Hollinger, Frances E et al. (2016) Inhibition of acetyl-CoA carboxylases by soraphen A prevents lipid accumulation and adipocyte differentiation in 3T3-L1 cells. Eur J Pharmacol 780:202-8
Yang, Junyi; Bindels, Laure B; Segura Munoz, Rafael R et al. (2016) Disparate Metabolic Responses in Mice Fed a High-Fat Diet Supplemented with Maize-Derived Non-Digestible Feruloylated Oligo- and Polysaccharides Are Linked to Changes in the Gut Microbiota. PLoS One 11:e0146144
Xie, Fang; Anderson, Christopher L; Timme, Kelsey R et al. (2016) Obesity-Dependent Increases in Oocyte mRNAs Are Associated With Increases in Proinflammatory Signaling and Gut Microbial Abundance of Lachnospiraceae in Female Mice. Endocrinology 157:1630-43
Natarajan, Sathish Kumar; Rasineni, Karuna; Ganesan, Murali et al. (2015) Structure, function and metabolism of hepatic and adipose tissue lipid droplets: implications in alcoholic liver disease. Curr Mol Pharmacol :
Shu, Jiang; Chiang, Kevin; Zempleni, Janos et al. (2015) Computational Characterization of Exogenous MicroRNAs that Can Be Transferred into Human Circulation. PLoS One 10:e0140587

Showing the most recent 10 out of 24 publications