Effects of Periodontal Pathogen on Insulin Secretion and Islet Cell Apoptosis

Background: Periodontitis is a chronic inflammatory condition that involves gingival and alveolar bone loss around teeth. Periodontitis is a host cell response to bacterial pathogens. Periodontal pathogens in time also disseminate from the oral cavity to other parts of the body, such as the liver, via systemic circulation. Epidemiologically, there is an association between Diabetes Mellitus and Periodontitis; patients that are comorbid with periodontitis and diabetes have marked severity in disease. However, the effect of periodontal pathogens on the development of insulin resistance and prediabetes has yet to be clarified. Results from previous animal studies indicate that induction of chronic periodontitis in both rat and mouse models caused increased insulin secretion (Hyperinsulinemia), Insulin Resistance (IR) and Glucose Intolerance (GI), all of which are classic hallmarks of prediabetes. This demonstrates that periodontitis plays a role in prediabetes. Thus, the hypothesis for this study was that a pancreatic beta cell line MIN6 exposed to Porphyromonas gingivalis (Pg), a gram negative anaerobic bacterial pathogen related to periodontitis, would cause 1. Increased insulin secretion, 2. Induce apoptosis after co-incubation in vitro and 3. Periodontitis induced by Pg in mice would also increase islet cell apoptosis in vivo. Material and Methods: MIN6 cells co-incubated with Pg for 0-17 hours were collected and assessed for insulin secretion, apoptosis, gene expression and protein expression using GSIS, ELISA, histochemistry, PCR and western blot. C57BL mice induced with periodontitis were evaluated from 0-22 weeks for fasting insulin level and pancreatic islet tissues from mice sacrificed at 23 weeks were subjected to histochemistry. Results: Co-incubation of Pg with MIN6 cells induced upregulation of INS1 and INS2 gene expression as well as insulin secretion in media with 5mM glucose conditions. In addition, Pg induced apoptosis via intrinsic and extrinsic pathways. Pg also downregulated AKT phosphorylation. To determine the effect of Pg on the pancreas, we induced chronic periodontitis by oral application of Pg and showed development of hyperinsulinemia by the 14th week. Apoptosis of islet cells were detected at sacrifice (23 weeks) in mice with periodontitis. Conclusion: This is the first report that a periodontal bacterial pathogen influences insulin secretion and also causes apoptosis of beta cells suggesting a potential mechanism by which periodontitis exacerbates the prediabetic condition.