{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T15:12:08Z","timestamp":1789053128091,"version":"build-2803163510"},"reference-count":46,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T00:00:00Z","timestamp":1636416000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Diabetes Invest"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Selenoprotein P (SeP, encoded by <jats:italic>SELENOP<\/jats:italic> in humans) is a hepatokine that causes insulin resistance in the liver and skeletal muscle. It was found that polyunsaturated fatty acid eicosapentaenoic acid (EPA) downregulates <jats:italic>Selenop<\/jats:italic> expression by inactivating SREBP\u20101c. The present study aimed to examine the effect of EPA for 12\u2009weeks on circulating SeP levels and insulin sensitivity in humans with type 2 diabetes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 20 participants with dyslipidemia and type 2 diabetes were randomly assigned to an EPA (900\u2009mg, twice daily) group and a control group. The primary endpoint was a change in serum SeP levels. Organ\u2010specific insulin sensitivity in the liver (HGP and %HGP), skeletal muscle (Rd), and adipose tissue (FFA and %FFA) were assessed using a hyperinsulinemic\u2010euglycemic clamp study with stable isotope\u2010labeled glucose infusion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Serum SeP levels were not changed in either group at the end of the study. In the EPA group, the changes in SeP levels were positively correlated with the change in serum EPA levels (<jats:italic>r<\/jats:italic>\u2009=\u20090.709, <jats:italic>P<\/jats:italic>\u2009=\u20090.022). Treatment with EPA significantly enhanced %FFA but not %HGP and Rd. The change in serum EPA levels was significantly positively correlated with the change in %HGP, and negatively correlated with changes in Rd.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The change in serum EPA levels was positively correlated with serum SeP levels, hepatic insulin sensitivity, and negatively with skeletal muscle insulin sensitivity in humans with type 2 diabetes. The EPA\u2010induced enhancement of hepatic insulin sensitivity might be associated with a mechanism independent of serum SeP levels.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdi.13699","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T23:12:42Z","timestamp":1634771562000},"page":"532-542","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Effects of eicosapentaenoic acid on serum levels of selenoprotein P and organ\u2010specific insulin sensitivity in humans with dyslipidemia and type 2 diabetes"],"prefix":"10.1111","volume":"13","author":[{"given":"Yumie","family":"Takeshita","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism Kanazawa University Graduate School of Medical Sciences Kanazawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chisato","family":"Teramura","sequence":"additional","affiliation":[{"name":"Department 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