{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T17:23:53Z","timestamp":1774632233304,"version":"3.50.1"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,6,1]],"date-time":"2016-06-01T00:00:00Z","timestamp":1464739200000},"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":["NIH\u2010NIDDK R21DKO76704"],"award-info":[{"award-number":["NIH\u2010NIDDK R21DKO76704"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P60DK020593\u20106"],"award-info":[{"award-number":["P60DK020593\u20106"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Xerostomia is defined as dry mouth resulting from a change in the amount or composition of saliva and is often a major oral health complication associated with diabetes mellitus (DM). Studies have shown that xerostomia is more common in females at the onset of DM. Evidence suggests that nitric oxide (NO) plays a critical role in healthy salivary gland function. However, the specific mechanisms by which NO regulates salivary gland function at the onset of DM have yet to be determined. This study has two aims: 1) to determine whether protein expression or dimerization of NO synthase enzymes (neuronal [nNOS] and endothelial [eNOS]) are altered in the onset of diabetic xerostomia; and 2) to determine whether the changes in nNOS\/eNOS protein expression or dimerization are correlated with changes in NO cofactor tetrahydrobiopterin (BH<jats:sub>4<\/jats:sub>) biosynthetic enzymes (guanosine triphosphate cyclohydrolase\u20101 and dihydrofolate reductase).<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Functional and Western blot studies were performed in streptozotocin\u2010induced and control Sprague\u2010Dawley female rats with DM (type 1 [t1DM]) using standardized protocols. Confirmation of xerostomia was determined by increased water intake and decreased salivary flow rate.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> The results showed that in female rats with DM, salivary hypofunction is correlated with decreased submandibular and parotid gland sizes. The results also show a decrease in NOS and BH<jats:sub>4<\/jats:sub> biosynthetic enzyme in submandibular glands.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> These results indicate that a decrease in submandibular NO\u2010BH<jats:sub>4<\/jats:sub> protein expression may provide insight pertaining to mechanisms for the development of hyposalivation in DM\u2010induced xerostomia. Furthermore, understanding the role of the NO\u2010BH<jats:sub>4<\/jats:sub> pathway may give insight into possible treatment options for the patient with DM experiencing xerostomia.<\/jats:p>","DOI":"10.1902\/jop.2016.150639","type":"journal-article","created":{"date-parts":[[2016,1,16]],"date-time":"2016-01-16T14:42:10Z","timestamp":1452955330000},"page":"735-741","source":"Crossref","is-referenced-by-count":26,"title":["Effects of Diabetes on Salivary Gland Protein Expression of Tetrahydrobiopterin and Nitric Oxide Synthesis and Function"],"prefix":"10.1002","volume":"87","author":[{"given":"Cassandra R.","family":"Stewart","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nneka","family":"Obi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elodie C.","family":"Epane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander A.","family":"Akbari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leslie","family":"Halpern","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janet H.","family":"Southerland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pandu R.","family":"Gangula","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,6]]},"reference":[{"key":"e_1_2_7_2_1","unstructured":"Diabetes: Symptoms Causes and Treatments 2015\u2010 Available at:http:\/\/www.medicalnewstoday.com\/info\/diabetes\/. 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