{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:22:48Z","timestamp":1791177768953,"version":"4.1.0"},"reference-count":80,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T00:00:00Z","timestamp":1754265600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005851","name":"Shahid Beheshti University of Medical Sciences","doi-asserted-by":"publisher","award":["43012221\u20101"],"award-info":[{"award-number":["43012221\u20101"]}],"id":[{"id":"10.13039\/501100005851","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Endocrino Diabet &amp;amp; Metabol"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Hypoxia is involved in the pathophysiology of type 2 diabetes (T2D), and oxygen therapy (hyperoxia) has been proposed for managing T2D. As a side effect, hyperoxia increases nitric oxide (NO) metabolism and decreases NO bioavailability. This study aims to investigate the effect of hyperoxia on NO synthases (NOSs), which produce NO from\n                      <jats:italic>L<\/jats:italic>\n                      \u2010arginine and arginase, which degrades\n                      <jats:italic>L<\/jats:italic>\n                      \u2010arginine in the soleus muscle (SM) of rats with T2D.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A combined high\u2010fat diet and a low dose of streptozotocin (30\u2009mg\/kg) were used to induce T2D in rats. Rats with T2D were divided into four groups (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20096\/group): Control rats exposed to normoxia (Control), control rats exposed to hyperoxia (C\u2009+\u2009HOX), diabetic rats exposed to normoxia (T2D) and diabetic rats exposed to hyperoxia (T2D\u2009+\u2009HOX). The hyperoxia and the control groups received 95% and 21% oxygen for 35\u2009days, respectively. SM was isolated at day 35, and the protein levels of endothelial NOS (eNOS), inducible NOS (iNOS), arginase, as well as tissue concentrations of lactate and NO metabolites (nitrate+nitrite\u2009=\u2009NOx) were measured.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compared to T2D, T2D\u2009+\u2009HOX rats had lower lactate concentration by 38% (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.009) and NOx concentration by 23% (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.011) in SM. In SM of rats with T2D, hyperoxia decreased eNOS protein by 46.2% (1.4\u2009\u00b1\u20090.13 vs. 2.6\u2009\u00b1\u20090.2\u2009ng\/mg protein,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002) and increased arginase protein by 2.3\u2010fold (1.04\u2009\u00b1\u20090.05 vs. 0.31\u2009\u00b1\u20090.07\u2009ng\/mg protein,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) but did not affect iNOS protein. Hyperoxia did not affect lactate concentration, eNOS and iNOS in SM of control rats but decreased NOx concentration by 25% (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.003).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Hyperoxia decreased NO bioavailability in SM of rats with T2D; this effect was associated with decreased eNOS and increased arginase protein levels. These findings suggest that oxygen therapy in diabetic rats may decrease NO bioavailability as a potential side effect.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/edm2.70090","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T09:18:59Z","timestamp":1754299139000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Effect of Hyperoxia on Nitric Oxide Metabolism in the Skeletal Muscle of Male Type 2 Diabetic Rats"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9099-174X","authenticated-orcid":false,"given":"Mahdis","family":"Mousavi","sequence":"first","affiliation":[{"name":"Endocrine Physiology Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences Shahid Beheshti University of Medical Sciences  Tehran 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