{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:51:32Z","timestamp":1790887892587,"version":"4.1.0"},"reference-count":21,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2016,6,23]],"date-time":"2016-06-23T00:00:00Z","timestamp":1466640000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Diabetes and Vascular Disease Research"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Endothelial dysfunction contributes to the development of vascular complication in diabetes. Arginase has emerged as a key mechanism behind endothelial dysfunction by its reciprocal regulation of nitric oxide production by substrate competition. We hypothesized that increased arginase activity in patients with type 2 diabetes shifts the metabolism of l-arginine from nitric oxide synthase to arginase resulting in an increase in the plasma ratio of ornithine\/citrulline, and that this ratio is associated with endothelial dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Forearm endothelium-dependent vasodilatation and endothelium-independent vasodilatation were determined in 15 patients with type 2 diabetes and 10 healthy controls and related to amino acids reflecting arginase and nitric oxide synthase activity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Compared to healthy controls, patients with diabetes had impaired endothelium-dependent vasodilatation and endothelium-independent vasodilatation. The ratios of ornithine\/citrulline and proline\/citrulline were 60% and 95% higher, respectively, in patients with diabetes than in controls ( p\u2009&lt;\u20090.001). The plasma ornithine\/arginine ratio was 36% higher in patients with diabetes, indicating increased arginase activity. These ratios were inversely correlated to endothelium-dependent vasodilatation and endothelium-independent vasodilatation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Patients with diabetes and macrovascular complications have increased amino acid ratios reflecting a shift in arginine metabolism due to arginase activation. These changes are inversely related to endothelial function supporting that arginase activity contributes to endothelial dysfunction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/1479164116643916","type":"journal-article","created":{"date-parts":[[2016,5,14]],"date-time":"2016-05-14T20:13:39Z","timestamp":1463256819000},"page":"354-360","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":50,"title":["Amino acid metabolism reflecting arginase activity is increased in patients with type 2 diabetes and associated with endothelial dysfunction"],"prefix":"10.1177","volume":"13","author":[{"given":"Oskar","family":"K\u00f6vamees","sequence":"first","affiliation":[{"name":"Unit of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden"},{"name":"Department of Cardiology Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey","family":"Shemyakin","sequence":"additional","affiliation":[{"name":"Unit of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden"},{"name":"Department of Cardiology Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Pernow","sequence":"additional","affiliation":[{"name":"Unit of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden"},{"name":"Department of Cardiology Karolinska University Hospital, Stockholm, 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