{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T13:15:21Z","timestamp":1768914921617,"version":"3.49.0"},"reference-count":43,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T00:00:00Z","timestamp":1694044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education, Science and Technological Development of the Republic of Serbia","award":["451-03-9\/2021-14\/200129"],"award-info":[{"award-number":["451-03-9\/2021-14\/200129"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Type 2 diabetes mellitus (T2DM) is associated with functional deterioration of the salivary gland and dental pulp, related to oxidative stress. The aim was to integrate experimental and bioinformatic findings to analyze the cellular mechanism of melatonin (MEL) action in the human parotid gland and dental pulp in diabetes. Human parotid gland tissue was obtained from 16 non-diabetic and 16 diabetic participants, as well as human dental pulp from 15 non-diabetic and 15 diabetic participants. In human non-diabetic and diabetic parotid gland cells (hPGCs) as well as in dental pulp cells (hDPCs), cultured in hyper- and normoglycemic conditions, glial cell line-derived neurotrophic factor (GDNF), MEL, inducible nitric oxide synthase (iNOS) protein expression, and superoxide dismutase (SOD) activity were measured by enzyme-linked immunosorbent assay (ELISA) and spectrophotometrically. Bioinformatic analysis was performed using ShinyGO (v.0.75) application. Diabetic participants had increased GDNF and decreased MEL in parotid (p &lt; 0.01) and dental pulp (p &lt; 0.05) tissues, associated with increased iNOS and SOD activity. Normoglycemic hDPCs and non-diabetic hPGCs treated with 0.1 mM MEL had increased GDNF (p &lt; 0.05), while hyperglycemic hDPCs treated with 1 mM MEL showed a decrease in up-regulated GDNF (p &lt; 0.05). Enrichment analyses showed interference with stress and ATF\/CREB signaling. MEL induced the stress-protective mechanism in hyperglycemic hDPCs and diabetic hPGCs, suggesting MEL could be beneficial for diabetes-associated disturbances in oral tissues.<\/jats:p>","DOI":"10.3390\/ijerph20186727","type":"journal-article","created":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T10:09:50Z","timestamp":1694081390000},"page":"6727","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Melatonin Action in Type 2 Diabetic Parotid Gland and Dental Pulp: In Vitro and Bioinformatic Findings"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2996-5450","authenticated-orcid":false,"given":"Milena","family":"Bara\u0107","sequence":"first","affiliation":[{"name":"Department of Pharmacology in Dentistry, Faculty of Dental Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6109-263X","authenticated-orcid":false,"given":"Milan","family":"Petrovi\u0107","sequence":"additional","affiliation":[{"name":"Clinic for Maxillofacial Surgery, Faculty of Dental Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nina","family":"Petrovi\u0107","sequence":"additional","affiliation":[{"name":"Vin\u010da Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8418-2395","authenticated-orcid":false,"given":"Nata\u0161a","family":"Nikoli\u0107-Jakoba","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Faculty of Dental Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0390-8789","authenticated-orcid":false,"given":"Zoran","family":"Aleksi\u0107","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Faculty of Dental Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0672-0693","authenticated-orcid":false,"given":"Lidija","family":"Todorovi\u0107","sequence":"additional","affiliation":[{"name":"Vin\u010da Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nata\u0161a","family":"Petrovi\u0107-Stanojevi\u0107","sequence":"additional","affiliation":[{"name":"Zvezdara University Medical Center, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"An\u0111eli\u0107-Jeli\u0107","sequence":"additional","affiliation":[{"name":"Zvezdara University Medical Center, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9828-0087","authenticated-orcid":false,"given":"Aleksandar","family":"Davidovi\u0107","sequence":"additional","affiliation":[{"name":"Zvezdara University Medical Center, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6225-7210","authenticated-orcid":false,"given":"Jelena","family":"Mila\u0161in","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Faculty of Dental Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2950-4056","authenticated-orcid":false,"given":"Jelena","family":"Roganovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmacology in Dentistry, Faculty of Dental Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.archoralbio.2016.01.002","article-title":"Is Salivary Gland Function Altered in Noninsulin-Dependent Diabetes Mellitus and Obesity\u2013Insulin Resistance?","volume":"64","author":"Ittichaicharoen","year":"2016","journal-title":"Arch. 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