Serpine1 Mediates Porphyromonas gingivalis Induced Insulin Secretion in the Pancreatic Beta Cell Line MIN6

Abstract

Periodontitis is an inflammatory disease resulting in destruction of gingiva and alveolar bone caused by an exuberant host immunological response to periodontal pathogens. Results from a number of epidemiological studies indicate a close association between diabetes and periodontitis. Results from cross-sectional studies indicate that subjects with periodontitis have a higher odds ratio of developing insulin resistance (IR). However, the mechanisms by which periodontitis influences the development of diabetes are not known. Results from our previous studies using an animal model of periodontitis suggest that periodontitis accelerates the onset of hyperinsulinemia and IR. In addition, LPS from a periodontal pathogen, Porphyromonas gingivalis (Pg), stimulates Serpine1 expression in the pancreatic beta cell line MIN6. Based on these observations, we hypothesized that a periodontal pathogen induces hyperinsulinemia and Serpine1 may be involved in this process. To test this hypothesis, we co-incubated Pg with the pancreatic beta cell line MIN6 and measured the effect on insulin secretion by MIN6 cells. We further determined the involvement of Serpine1 in insulin secretion by downregulating Serpine1 expression. Our results indicated that Pg stimulated insulin secretion by approximately 3.0 fold under normoglycemic conditions. In a hyperglycemic state, Pg increased insulin secretion by 1.5 fold. Pg significantly upregulated expression of the Serpine1 gene and this was associated with increased secretion of insulin by MIN6 cells. However, cells with downregulated Serpine1 expression were resistant to Pg stimulated insulin secretion under normoglycemic conditions. We conclude that the periodontal pathogen, Pg, induced insulin secretion by MIN6 cells and this induction was, in part, Serpine1 dependent. Thus, Serpine1 may play a pivotal role in insulin secretion during the accelerated development of hyperinsulinemia and the resulting IR in the setting of periodontitis.

Host insulin resistance caused by Porphyromonas gingivalis-review of recent progresses

“…Type 2 diabetes is a metabolic disease that is a major public health problem worldwide. The bidirectional association between periodontitis and diabetes has been widely accepted ( Lalla and Papapanou, 2011 ).Results of cross-sectional studies have shown that patients with periodontitis have a higher incidence of insulin resistance (IR) ( Bhat and Watanabe, 2015 ). Insulin resistance is an important cause of type 2 diabetes mellitus (T2DM) ( Tian et al., 2020 ).…”

Links between Insulin Resistance and Periodontal Bacteria: Insights on Molecular Players and Therapeutic Potential of Polyphenols

“…In animal models, periodontitis induction is associated with hyperinsulinemia [90], suggesting a direct impact of periodontal bacteria on the function of pancreatic β-cells, the only known source of circulating insulin. In the murine pancreatic β-cell line MIN6, P. gingivalis and its LPS induce an increase in insulin secretion [108] associated with the elevation of SerpinE1 gene expression [109]. The serpinE1 gene encodes the plasminogen activator inhibitor-1 (PAI-1), which is known to increase during obesity, insulin resistance and diabetes [110].…”