Department of Pharmacology in Dentistry, Faculty of Dental Medicine, University of Belgrade, 11000 Belgrade, Serbia.
Clinic for Maxillofacial Surgery, Faculty of Dental Medicine, University of Belgrade, 11000 Belgrade, Serbia.
Int J Environ Res Public Health. 2023 Sep 7;20(18):6727. doi: 10.3390/ijerph20186727.
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 ( < 0.01) and dental pulp ( < 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 ( < 0.05), while hyperglycemic hDPCs treated with 1 mM MEL showed a decrease in up-regulated GDNF ( < 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.
2 型糖尿病（T2DM）与唾液腺和牙髓功能恶化有关，这与氧化应激有关。目的是整合实验和生物信息学发现，分析褪黑素（MEL）在糖尿病患者腮腺和牙髓中的细胞作用机制。从 16 名非糖尿病和 16 名糖尿病参与者中获得人腮腺组织，以及从 15 名非糖尿病和 15 名糖尿病参与者中获得人牙髓组织。在高血糖和正常血糖条件下培养的人非糖尿病和糖尿病腮腺细胞（hPGCs）以及牙髓细胞（hDPCs）中，通过酶联免疫吸附试验（ELISA）和分光光度法测量胶质细胞系衍生的神经营养因子（GDNF）、MEL、诱导型一氧化氮合酶（iNOS）蛋白表达和超氧化物歧化酶（SOD）活性。使用 ShinyGO（v.0.75）应用程序进行生物信息学分析。糖尿病参与者的腮腺（<0.01）和牙髓（<0.05）组织中 GDNF 增加，MEL 减少，与 iNOS 和 SOD 活性增加有关。用 0.1mM MEL 处理的正常血糖 hDPCs 和非糖尿病 hPGCs 中 GDNF 增加（<0.05），而用 1mM MEL 处理的高血糖 hDPCs 中上调的 GDNF 减少（<0.05）。富集分析显示对应激和 ATF/CREB 信号的干扰。MEL 在高血糖 hDPCs 和糖尿病 hPGCs 中诱导应激保护机制，表明 MEL 可能有益于糖尿病相关的口腔组织紊乱。
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