{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T21:19:22Z","timestamp":1777497562866,"version":"3.51.4"},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,1,11]],"date-time":"2017-01-11T00:00:00Z","timestamp":1484092800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK067223"],"award-info":[{"award-number":["R01DK067223"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2017,3]]},"abstract":"Summary<\/jats:title>\n \n Erectile dysfunction (\n ED<\/jats:styled-content>\n ) associated with type 2 diabetes mellitus (T2\n DM<\/jats:styled-content>\n ) involves dysfunctional nitric oxide (\n NO<\/jats:styled-content>\n ) signaling and increased oxidative stress in the penis. However, the mechanisms of endothelial\n NO<\/jats:styled-content>\n synthase (e\n NOS<\/jats:styled-content>\n ) and neuronal\n NO<\/jats:styled-content>\n synthase (n\n NOS<\/jats:styled-content>\n ) dysregulation, and the sources of oxidative stress, are not well defined, particularly at the human level. The objective of this study was to define whether uncoupled e\n NOS<\/jats:styled-content>\n and n\n NOS<\/jats:styled-content>\n , and\n NADPH<\/jats:styled-content>\n oxidase upregulation, contribute to the pathogenesis of\n ED<\/jats:styled-content>\n in T2\n DM<\/jats:styled-content>\n men. Penile erectile tissue was obtained from 9 T2\n DM<\/jats:styled-content>\n patients with\n ED<\/jats:styled-content>\n who underwent penile prosthesis surgery for\n ED<\/jats:styled-content>\n , and from six control patients without T2\n DM<\/jats:styled-content>\n or\n ED<\/jats:styled-content>\n who underwent penectomy for penile cancer. The dimer\u2010to\u2010monomer protein expression ratio, an indicator of uncoupling for both e\n NOS<\/jats:styled-content>\n and n\n NOS<\/jats:styled-content>\n , total protein expressions of e\n NOS<\/jats:styled-content>\n and n\n NOS<\/jats:styled-content>\n , as well as protein expressions of\n NADPH<\/jats:styled-content>\n oxidase catalytic subunit gp91phox (an enzymatic source of oxidative stress) and 4\u2010hydroxy\u20102\u2010nonenal [4\u2010\n HNE<\/jats:styled-content>\n ] and nitrotyrosine (markers of oxidative stress) were measured by western blot in this tissue. In the erectile tissue of T2\n DM<\/jats:styled-content>\n men, e\n NOS<\/jats:styled-content>\n and n\n NOS<\/jats:styled-content>\n uncoupling and protein expressions of\n NADPH<\/jats:styled-content>\n oxidase subunit gp91phox, 4\u2010\n HNE<\/jats:styled-content>\n \u2010 and nitrotyrosine\u2010modified proteins were significantly (\n p<\/jats:italic>\n \u00a0<\u00a00.05) increased compared to control values. Total e\n NOS<\/jats:styled-content>\n and n\n NOS<\/jats:styled-content>\n protein expressions were not significantly different between the groups. In conclusion, mechanisms of T2\n DM<\/jats:styled-content>\n \u2010associated\n ED<\/jats:styled-content>\n in the human penis may involve uncoupled e\n NOS<\/jats:styled-content>\n and n\n NOS<\/jats:styled-content>\n and\n NADPH<\/jats:styled-content>\n oxidase upregulation. Our description of molecular factors contributing to the pathogenesis of T2\n DM<\/jats:styled-content>\n \u2010associated\n ED<\/jats:styled-content>\n at the human level is relevant to advancing clinically therapeutic approaches to restore erectile function in T2DM patients.\n <\/jats:p>","DOI":"10.1111\/andr.12313","type":"journal-article","created":{"date-parts":[[2017,1,11]],"date-time":"2017-01-11T17:29:40Z","timestamp":1484155780000},"page":"294-298","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Constitutive\n NOS<\/scp>\n uncoupling and\n NADPH<\/scp>\n oxidase upregulation in the penis of type 2 diabetic men with erectile dysfunction"],"prefix":"10.1111","volume":"5","author":[{"given":"B.","family":"Musicki","sequence":"first","affiliation":[{"name":"The James Buchanan Brady Urological Institute and Department of Urology The Johns Hopkins School of Medicine Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. L.","family":"Burnett","sequence":"additional","affiliation":[{"name":"The James Buchanan Brady Urological Institute and Department of Urology The Johns Hopkins School of Medicine Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,1,11]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2011.03.024"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1743-6109.2009.01587.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2001.4874"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2014.07.046"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2008.09.005"},{"key":"e_1_2_8_7_1","first-page":"273","article-title":"Erectile dysfunction in young non\u2010obese type II diabetic Goto\u2010Kakizaki rats is associated with decreased eNOS phosphorylation at 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