Abstract
Selenium is an essential trace element in the diet of mammals which is important for many physiological functions. However, a number of epidemiological studies have suggested that high selenium status is a possible risk factor for the development of type 2 diabetes, although they cannot distinguish between cause and effect. Selenoprotein P (Sepp1) is central to selenium homeostasis and widely expressed in the organism. Here we review the interaction between Sepp1 and glucose metabolism with an emphasis on experimental evidence. In models with or without gene modification, glucose and insulin can regulate Sepp1 expression in the pancreas and liver, and vice versa. Especially in the liver, Sepp1 is regulated virtually like a gluconeogenic enzyme. Combining these data suggests that there could be a feedback regulation between hepatic Sepp1 and pancreatic insulin and that increasing circulating Sepp1 might be the result rather than the cause of abnormal glucose metabolism. Future studies specifically designed to overexpress Sepp1 are needed in order to provide a more robust link between Sepp1 and type 2 diabetes.
Highlights
Selenium is an essential trace element in the diet of mammals
Despite the expectation that selenium might prevent the development of diabetes owing to its antioxidant and insulin-mimetic properties [6,7,8], in recent years, some epidemiological studies, including cross-sectional studies and longitudinal studies, have shown that supranutritional selenium intake or high plasma selenium levels are a possible risk factor for the development of type 2 diabetes or metabolic syndrome [9,10,11,12]
In the prospective observational Epidemiology of Vascular Ageing (EVA) study, 1162 participants with complete data were analyzed and it was found that high plasma selenium correlated with a decreased risk of onset of hyperglycaemia during a 9-year follow-up period in elderly men [14]
Summary
Selenium is an essential trace element in the diet of mammals. While its importance for the brain [1], fertility [2], immune [3] and thyroid functions [4] and cancer prevention [5] is well established, Nutrients 2013, 5 the association between selenium and glucose metabolism is conflicting. Misu et al studied the role of Sepp in the regulation of glucose metabolism and insulin sensitivity in KKAy mice, a model of type 2 diabetes and obesity; knockdown of Sepp by siRNA injection resulted in a 30% reduction in Sepp protein levels in the liver and blood and improved both glucose intolerance and insulin resistance [42]. We hypothesize that there could be a feedback regulation between hepatic Sepp and pancreatic insulin: in the normal organism, circulating high-glucose concentration stimulates the expression of insulin in the pancreas and Sepp in the liver. The increasing Sepp is transported into the pancreas and may collaterally enhance insulin production, as glucose tolerance tests revealed that blood insulin levels were significantly elevated at 0 min in SEPP1-injected mice in the study of Misu and colleagues [42]. We think that the increase in circulating Sepp could be the result rather than the cause of abnormal glucose metabolism
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
