Inorganic Se compounds account for only a small fraction of total Se naturally occurring in foods. Far more abundant are organic compounds such as selenomethionine and Se-methylselenocysteine (SMSC). In the Selenium and Vitamin E Cancer Prevention Trial (SELECT), a high dose of selenomethionine was given to subjects, most of whom began the study with high Se status

[14]. Such supplementation resulted in a minimal but statistically significant increase in risk of type II diabetes [14]. The choice of SMSC for use in this study is based on (a) its significant contribution to total Se in foods, particularly in those foods of high total Se content; (b) its high biological availability; (c) its demonstrated ability to induce selenoenzyme activity and increase other markers of Se status; (d) chemopreventive efficacy, Alectinib which is superior to that of selenomethionine; (e) its low toxicity in comparison with other Se forms; (f) its noninvolvement in protein synthesis, unlike selenomethionine, which is incorporated nonspecifically into proteins in place of methionine and thus diverted from Se metabolic pathways;

and (g) the paucity of data concerning effects on glucose metabolism of this Se form, which is demonstrably relevant and significant in human nutrition. Dasatinib price Elucidating the mechanisms through which supplemental Se affects glucose metabolism, particularly Janus kinase (JAK) forms of Se that are commonly found in food, is an important step in understanding the associated risk of Se supplementation. Recent work by Misu et al [15] has shown that Se-induced

changes in glucose metabolism may occur by reducing basal activation of AMPK. If Se is to be useful as an anticancer supplement without increasing the risk of metabolic diseases associated with IR, it may be necessary to couple it with other factors that limit these potential complications. Isoflavones (IF) are estrogen-like compounds found primarily in soy. Increased dietary IF cause favorable adaptations in glucose metabolism [16]. Interestingly, there is growing evidence that these changes may be facilitated via increased AMPK activation [17]. Isoflavones are also reported to cause a reduction in body fat that is likely mediated by increased energy metabolism [18]. Thus, increasing IF consumption may be an effective approach to help prevent or limit the potentially negative impact of Se supplementation on glucose management. Therefore, due to differences in metabolic responses to increased IF and Se, we hypothesized that (1) a chronic increase in SMSC consumption would lead to impaired glucose control, (2) a high IF (HIF) diet would improve glucose control, and (3) if HIF diet was consumed with high SMSC, the negative effects on glucose management associated with Se supplementation would be attenuated.