Salivary gland dysfunction is a common complication of diabetes. Decreased saliva production and changes in saliva composition may cause oral diseases. Reactive oxygen species (ROS) generation in the salivary glands results in the loss of acinar cells and decreased saliva secretion. Glucagon-like peptide 1 (GLP-1) is the incretin hormone that regulates blood glucose level and can suppress ROS production and inflammation through its antioxidant effects. Dipeptidyl peptidase-4 (DPP-4) is an enzyme that breaks down GLP-1. In this study, we evaluated the pathological role of DPP-4 and GLP-1 on salivary gland dysfunction in type 2 diabetic db/db mice. We observed reduced salivary secretion and histopathological alteration of salivary glands in the db/db mice. The increased DPP-4 and decreased GLP-1 levels in the salivary glands were also detected in the db/db mice. Furthermore, the db/db mice had increased apoptosis and oxidative injury in salivary glands. There was an accumulation of advanced glycation end products and mucus in the salivary glands of the db/db mice. In conclusion, these results showed the possible involvement of DPP-4 and GLP-1, leading to increased ROS-induced apoptosis in diabetes-related salivary gland dysfunction. DPP-4 and GLP-1 may be a pharmacological target for patients with diabetes-related salivary gland dysfunction.

Declined salivary gland function is commonly observed in patients with diabetes. Advanced glycation end products (AGEs) are believed to contribute to the pathogenesis of diabetes-induces hypofunction of the salivary glands. Polydatin (resveratrol-3-O-β-mono-D-glucoside) is a polyphenol that can be easily accessed from peanut, grape, and red wines. Although polydatin is known to have anti-glycation, anti-oxidation, and anti-inflammation effects, its effect in the salivary gland is not known. In the present study, we evaluated the AGEs burden in the salivary gland in streptozotocin (STZ)-induced diabetic rats and the protective effect of polydatin on diabetes-related salivary hypofunction. Polydatin (50 and 100 mg/kg/day) was orally administered in the STZ-induced diabetic rats for 4 weeks. The results showed that the salivary flow rate of the STZ-induced diabetic rats was reduced compared with that in the normoglycemic control rats. The circulating AGEs in serum and secreted AGEs in saliva increased in the STZ-induced diabetic rats. The reactive oxygen specises (ROS) were highly generated in the salivary gland in these diabetic rats. The salivary gland from the diabetic rats showed increased acinar cell apoptosis compared to normoglycemic control mice. However, polydatin suppressed all of these diabetes-related salivary changes. Overall, polydatin could provide a beneficial option for diabetes-related salivary hypofunction.