Insulin Response Genes in Different Stages of Periodontal Disease CL INICaL INv eS TIGaT IONS

Bacterial infections are known to alter glucose metabolism within tissues via mechanisms of inflammation. We conducted this study to examine whether insulin response genes are differentially expressed in gingival tissues, comparing samples from experimental gingivitis and peri- odontitis subjects to those from healthy individuals. Total RNA was extracted from gingival biopsies from 26 partici- pants: 8 periodontally healthy, 9 exper- imental gingivitis, and 9 periodonti- tis subjects. Gene expression patterns were evaluated with a polymerase chain reaction array panel to exam- ine 84 candidate genes involved with glucose metabolism, insulin resistance, and obesity. Array data were evalu- ated with a t test adjusted by the false discover rate (P < 0.05), and ingenu- ity pathway analysis was performed for statistical testing of pathways. Although tissue samples were not sufficient to enable protein quantification, we con- firmed the upregulation of the key gene using lipopolysaccharide-stimulated primary gingival epithelial cells by Western blot. The mRNA expression pat- terns of genes that are associated with insulin response and glucose metabo- lism are markedly different in exper- imental gingivitis subjects compared with healthy controls. Thirty-two genes are upregulated significantly by at least 2-fold, adjusted for false discover rate (P < 0.05). Periodontitis subjects show similar but attenuated changes in gene expression patterns, and no genes meet the significance criteria. Ingenuity pathway analysis demonstrates signif- icant activation of the carbohydrate metabolism network in experimen- tal gingivitis but not in periodontitis. G6PD protein increases in response to lipopolysaccharide stimulation in pri- mary gingival epithelial cells, which is in the same direction as upregulated mRNA in tissues. Acute gingival inflam- mation may be associated with tissue metabolism changes, but these changes are not evident in chronic periodonti- tis. This study suggests that acute gin- gival inflammation may induce local- ized changes that modify tissue insulin/ glucose metabolism.