Increased inflammation, disturbed extracellular matrix remodeling and reduced parotid and submandibular salivary gland function in male Wistar rats with type 2 diabetes

BACKGROUND: Insulin-independent type 2 diabetes mellitus (DM2) causes numerous organ complications, some of which involve the oral cavity. However, to date, the causes of reduced salivary secretion in patients with DM2 remain unclear. OBJECTIVES: The present study is the first to evaluate the salivary inflammatory and anti-inflammatory profiles in the salivary glands of rats with DM2. MATERIAL AND METHODS: Twenty male Wistar Cmdb:WI rats were randomly divided into 2 groups: a control group and a DM2 group. Type 2 diabetes mellitus was induced by feeding the rats a high-fat diet and administering a single intraperitoneal injection of low-dose streptozotocin (35 mg/kg bw). Salivary gland function was evaluated using pilocarpine-stimulated salivary flow rate and α-amylase activity. The salivary inflammatory profile was assessed using a multiplex enzyme-linked immunosorbent assay (ELISA). RESULTS: Type 2 diabetes mellitus caused dysfunction of the parotid glands (PGs) and submandibular glands (SMGs), manifested by a reduction in the salivary flow rate and a decrease in salivary α-amylase activity. In DM2 rats, significantly higher levels of pro-inflammatory cytokines (interleukin (IL)-1α, tumor necrosis factor alpha (TNF-α), IL-6, IL-7, IL18), anti-inflammatory cytokines (IL-10), Th1 (IL-12) and Th17 (IL-17) cytokines, chemokines (monocyte chemoattractant protein (MCP)-1α/chemokine ligand 3 (CCL3), macrophage inflammatory protein (MIP)-1α/CCL3, regulated on activation, normal T-cell expressed and secreted chemokine (RANTES)/CCL5, MIP-3α/CCL20, growth-regulated oncogene (GRO)-1α/CCL1), and growth factors (macrophage colony-stimulating factor (M-CSF), granulocyte macrophage colony stimulating factor (GM-CSF) and vascular endothelial growth factor (VEGF)) were observed, as well as increased activity of salivary pro-inflammatory enzymes (myeloperoxidase (MPO), β-D-glucuronidase (GLU)). Evaluation of the inflammatory profile did not indicate the dominance of any branch of the immune system, with the PG being the main source of salivary cytokines, chemokines and growth factors. The activity of lysosomal exoglycosidases and extracellular matrix metalloproteinases (MMPs) involved in salivary gland remodeling was significantly higher in the PGs and SBGs of DM2 rats compared with controls. CONCLUSIONS: Increased levels of salivary inflammatory biomarkers accompanied by decreased salivary secretory function may indicate the contribution of inflammation to salivary gland dysfunction. During the course of DM2, impairment predominantly affects PGs.