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

Uppoor G Bhat ,Keiko Watanabe

doi:10.13188/2377-987x.1000008

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.

Highlights

Periodontitis is a destruction of gingiva and alveolar bone that affects approximately 50% of population in the US [1]
We previously investigated the effect of Porphyromonas gingivalis (Pg) LPS on insulin secretion using the pancreatic beta cell line MIN6 [11]
The results indicated that Pg LPS augments insulin secretion from MIN6 cells under a normoglycemic, but not hyperglycemic conditions and that Serpine 1 expression increases in response to Pg LPS

Summary

Introduction

Periodontitis is a destruction of gingiva and alveolar bone that affects approximately 50% of population in the US [1]. In response to insulin signaling impairment, and subsequent insensitivity to insulin, pancreatic beta cells produce higher levels of insulin (hyperinsulinemia). This is a widely accepted pathway of IR development. Whether the hyperinsulinemia in animals with periodontitis is in response to impaired insulin signaling in insulin target organs and/or some other factor such as periodontal pathogens stimulating insulin secretion is not known. The results indicate that Pg LPS stimulates insulin secretion by MIN6 cells [11], further supporting the concept that periodontal pathogens influence IR. ISSN: 2377-987X influences insulin secretion, we determined the effect of Pg on insulin secretion and a possible involvement of Serpine on the Pg induced insulin secretion in the pancreatic beta-cell line MIN6

Methods

Results

Discussion