Induction of diabetes to PAR2-deficient (PAR2<sup>-/-</sup>) mice did not affect endothelial function and eNOS<sup>Ser1177</sup> phosphorylation in the aorta compared with non-diabetic PAR2<sup>-/-</sup> mice.
Accordingly, insulin may impact the therapeutic effects of carboxylesterases substrate drugs and also inhibit expression of other genes targeted by PXR, thus inducing a wide range of potential drug-drug interactions (DDIs) during the treatment of diabetes.
A Poisson regression model showed that histories of diabetes and hypertension were associated with a larger number of teeth with a PPD ≥5 mm (diabetes: prevalence rate ratio [PRR] 1.36, 95% confidence interval [CI] 1.00-1.85; hypertension: PRR 1.27, 95% CI 1.02-1.58) after adjusting for potential periodontal risk factors.
Increasing evidences have suggested that PPAR, FXR, LXR ,PXR and CAR are involved in the development of diabetes and its complications through different mechanisms, including the regulation of glucose and lipid metabolism, insulin and inflammation response and related others.
Notably, much experimental and clinical evidence show that PXR senses xenobiotics and triggers the detoxification response to prevent diseases such as diabetes, obesity, intestinal inflammatory diseases and liver fibrosis.
Future studies are necessary to elucidate the effects of PAR1 upregulation in periodontally healthy sites and PAR2 downregulation in chronic periodontitis sites on the increased susceptibility and severity of periodontitis in diabetes.