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Insights into the function of vanins have evolved lately, indicating vanin-1 to play a role in inflammation, oxidative stress and cell migration. Moreover, vanin-1 has recently gained attention as a novel modulator of hepatic glucose and lipid metabolism. In the present study, we investigated the role of vanin-1 in the development of hepatic steatosis and insulin resistance in animal models of obesity and diabetes. In addition, we evaluated the potency of RR6, a novel pharmacological vanin-1 inhibitor, as an anti-diabetic drug. Increased vanin activity was observed in plasma and liver of high fat diet (HFD)-induced obese mice, as well as ZDF-diabetic rats. Ablation of vanin-1 (<jats:italic>Vnn1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice) mildly improved glucose tolerance and insulin sensitivity in HFD-fed mice, but had no effects on body weight, hepatic steatosis or circulating lipid levels. Oral administration of RR6 for 8 days completely inhibited plasma vanin activity, but did not affect hepatic glucose production, insulin sensitivity or hepatic steatosis in ZDF-diabetes rats. In conclusion, absence of vanin-1 activity improves insulin sensitivity in HFD-fed animals, yet short-term inhibition of vanin activity may have limited value as an anti-diabetic strategy.<\/jats:p>","DOI":"10.1038\/srep21906","type":"journal-article","created":{"date-parts":[[2016,3,2]],"date-time":"2016-03-02T12:06:17Z","timestamp":1456920377000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Genetic and pharmacological inhibition of vanin-1 activity in animal models of type 2 diabetes"],"prefix":"10.1038","volume":"6","author":[{"given":"Janna A.","family":"van Diepen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick A.","family":"Jansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dov B.","family":"Ballak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anneke","family":"Hijmans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floris P.J.T.","family":"Rutjes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cees J.","family":"Tack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihai G.","family":"Netea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joost","family":"Schalkwijk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rinke","family":"Stienstra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,3,2]]},"reference":[{"key":"BFsrep21906_CR1","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1016\/j.jhep.2014.04.013","volume":"61","author":"JA van Diepen","year":"2014","unstructured":"van Diepen, J. 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