{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T02:04:34Z","timestamp":1792029874716,"version":"4.4.0"},"reference-count":62,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,2,3]],"date-time":"2021-02-03T00:00:00Z","timestamp":1612310400000},"content-version":"vor","delay-in-days":33,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004595","name":"Universiti Sains Malaysia","doi-asserted-by":"publisher","award":["1001\/PPSP\/8012221"],"award-info":[{"award-number":["1001\/PPSP\/8012221"]}],"id":[{"id":"10.13039\/501100004595","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p>Diabetes mellitus contributes to macro\u2010 and microvascular complications, leading to adverse cardiovascular events. This study examined the effects of vitamin D deficiency on the vascular function and tissue oxidative status in the microcirculation of diabetic rats and to determine whether these effects can be reversed with calcitriol (active vitamin D metabolite) supplementation. Streptozotocin\u2010induced diabetic rats were fed for 10 weeks with control diet (DC) or vitamin D\u2010deficient diet without (DD) or with oral calcitriol supplementation (0.15\u2009<jats:italic>\u03bc<\/jats:italic>g\/kg) in the last four weeks (DDS) (10 rats each group). A nondiabetic rat group that received control diet was also included (NR). After 10 weeks, rats were sacrificed; mesenteric arterial rings with and without endothelium were studied using wire myograph. Western blotting of the mesenteric arterial tissue was performed to determine the protein expression of endothelial nitric oxide synthase (eNOS) enzyme. Antioxidant enzyme superoxide dismutase (SOD) activity and oxidative stress marker malondialdehyde (MDA) levels in the mesenteric arterial tissue were also measured. The DC group had significantly lower acetylcholine\u2010induced relaxation and augmented endothelium\u2010dependent contraction, with reduced eNOS expression, compared to NR rats. In mesenteric arteries of DD, acetylcholine\u2010induced endothelium\u2010dependent and sodium nitroprusside\u2010induced endothelium\u2010independent relaxations were lower than those in DC. Calcitriol supplementation in DDS restored endothelium\u2010dependent relaxation. Mesenteric artery endothelium\u2010dependent contraction of DD was greater than DC; it was not affected by calcitriol supplementation. The eNOS protein expression and SOD activity were significantly lower while MDA levels were greater in DD compared to DC; these effects were not observed in DDS that received calcitriol supplementation. In conclusion, vitamin D deficiency causes eNOS downregulation and oxidative stress, thereby impairing the vascular function and posing an additional risk for microvascular complications in diabetes. Calcitriol supplementation to diabetics with vitamin D deficiency could potentially be useful in the management of or as an adjunct to diabetes\u2010related cardiovascular complications.<\/jats:p>","DOI":"10.1155\/2021\/3109294","type":"journal-article","created":{"date-parts":[[2021,2,3]],"date-time":"2021-02-03T20:51:49Z","timestamp":1612385509000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Calcitriol Supplementation Ameliorates Microvascular Endothelial Dysfunction in Vitamin D\u2010Deficient Diabetic Rats by Upregulating the Vascular eNOS Protein Expression and Reducing Oxidative Stress"],"prefix":"10.1155","volume":"2021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2813-1948","authenticated-orcid":false,"given":"Chee Lee","family":"Wee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siti Safiah","family":"Mokhtar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirnpal Kaur Banga","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9469-4231","authenticated-orcid":false,"given":"Sahran","family":"Yahaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan Wai Sum","family":"Leung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5418-953X","authenticated-orcid":false,"given":"Aida Hanum Ghulam","family":"Rasool","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,2,3]]},"reference":[{"key":"e_1_2_9_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.10058"},{"key":"e_1_2_9_2_2","volume-title":"IDF Diabetes Atlas","author":"International Diabetes Federation","year":"2019"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.5694\/j.1326-5377.2003.tb05655.x"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/MOL.0b013e328011c6fc"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra070553"},{"key":"e_1_2_9_6_2","doi-asserted-by":"publisher","DOI":"10.1592\/phco.29.6.691"},{"key":"e_1_2_9_7_2","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.27.12.2813"},{"key":"e_1_2_9_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.706127"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2010.02.021"},{"key":"e_1_2_9_10_2","doi-asserted-by":"publisher","DOI":"10.3343\/alm.2013.33.2.156"},{"key":"e_1_2_9_11_2","doi-asserted-by":"publisher","DOI":"10.3390\/nu6125419"},{"key":"e_1_2_9_12_2","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.2741"},{"key":"e_1_2_9_13_2","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.29.01.06.dc05-1876"},{"key":"e_1_2_9_14_2","article-title":"Molecular mechanism of vasoprotective effects of Vitamin D","volume":"7","author":"Melaku L.","year":"2018","journal-title":"International Journal of Health & Allied Sciences"},{"key":"e_1_2_9_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2012.12.013"},{"key":"e_1_2_9_16_2","doi-asserted-by":"publisher","DOI":"10.4103\/2230-8210.190558"},{"key":"e_1_2_9_17_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000539-200104000-00035"},{"key":"e_1_2_9_18_2","doi-asserted-by":"publisher","DOI":"10.2174\/1381612033453866"},{"key":"e_1_2_9_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2005.05.019"},{"key":"e_1_2_9_20_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-1212"},{"key":"e_1_2_9_21_2","article-title":"The effect of calcitriol on lipid profile and oxidative stress in hyperlipidemic patients with type 2 diabetes mellitus","volume":"10","author":"Eftekhari M. 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