Expression of Glucagon-Like Peptide-1 Receptors in the Submandibular Gland of Mice and Its Implications in Type 2 Diabetes.

Introduction Type 2 diabetes mellitus (T2DM) not only affects the pancreas directly involved in glucose metabolism but also impairs salivary gland function. Glucagon-like peptide-1 (GLP-1) is a gastrointestinal hormone that lowers postprandial blood glucose levels by stimulating insulin secretion from the pancreas. Previous studies have revealed the presence of GLP-1 receptors (GLP-1R) in salivary glands. However, the effect of diabetes on salivary gland GLP-1R remains unclear. This study aimed to observe the impact of T2DM on GLP-1R in the submandibular gland (SMG). Materials and methods Twenty-five-week-old mice were randomly divided into four groups (n=5 each): 11w and 13w control groups (CON), and 11w and 13w diabetes mellitus groups (DM). After a five-day adaptation period, the DM group mice were subjected to a high-fat diet, while the CON group received a standard diet. The DM group mice were then induced into a state of T2DM by a single low-dose streptozotocin injection at nine weeks of age. Oral glucose tolerance tests (OGTT) were conducted to evaluate mouse glucose tolerance. At 11 and 13 weeks of age, SMG was excised under general anesthesia, and the morphology of SMG was evaluated by hematoxylin-eosin staining, while the distribution and expression of GLP-1R were assessed by immunohistochemical staining. The data obtained were subjected to the Shapiro-Wilk test to confirm normal distribution, the t-test for the OGTT results, and statistical analysis for other results by one-way analysis of variance. Results Consistent with previous reports, the mice in the DM group showed higher body weight and lower glucose tolerance. Histological analysis revealed an increase in the acinar area and a decrease in the ductal area of the SMG in the DM group. Although there was no significant decrease in the cell count regarding the ductal area, a tendency toward luminal dilation was observed. Interestingly, the expression pattern of GLP-1R was limited to the ductal portion of the SMG, with a decrease in anti-GLP-1R-positive areas observed in the DM group compared to the CON group. While there was no significant difference in anti-GLP-1R-positive areas between the CON11w and CON13w groups, the DM13w group exhibited a significant decrease compared to the DM11w group. These data suggest that diabetes induces both structural changes in the SMG and a reduction in GLP-1R expression, particularly in the ductal regions. Conclusions We found that the expression level of GLP-1R in SMG was decreased in the DM group mice. This data demonstrates the potential relationship between T2DM and GLP-1R expression. Moreover, there was an indication of a temporal decrease in anti-GLP-1R positive areas over time. This result may suggest the involvement of salivary gland GLP-1R in the mechanism of impaired SMG function caused by T2DM, potentially mediated through the decrease in blood GLP-1 levels.