Insulin Response Genes in Different Stages of Periodontal Disease.
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 periodontitis subjects to those from healthy individuals. Total RNA was extracted from gingival biopsies from 26 participants: 8 periodontally healthy, 9 experimental gingivitis, and 9 periodontitis subjects. Gene expression patterns were evaluated with a polymerase chain reaction array panel to examine 84 candidate genes involved with glucose metabolism, insulin resistance, and obesity. Array data were evaluated with a t test adjusted by the false discover rate (P < 0.05), and ingenuity pathway analysis was performed for statistical testing of pathways. Although tissue samples were not sufficient to enable protein quantification, we confirmed the upregulation of the key gene using lipopolysaccharide-stimulated primary gingival epithelial cells by Western blot. The mRNA expression patterns of genes that are associated with insulin response and glucose metabolism are markedly different in experimental 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 significant activation of the carbohydrate metabolism network in experimental gingivitis but not in periodontitis. G6PD protein increases in response to lipopolysaccharide stimulation in primary gingival epithelial cells, which is in the same direction as upregulated mRNA in tissues. Acute gingival inflammation may be associated with tissue metabolism changes, but these changes are not evident in chronic periodontitis. This study suggests that acute gingival inflammation may induce localized changes that modify tissue insulin/glucose metabolism.
Center for Oral and Systemic Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Oral Biology Curriculum, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
N
N
Yu
Center for Oral and Systemic Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Department of Periodontology, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
S P
SP
Barros
Center for Oral and Systemic Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
S
S
Zhang
Center for Oral and Systemic Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
K L
KL
Moss
Center for Oral and Systemic Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
S T
ST
Phillips
Center for Oral and Systemic Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Department of Periodontology, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA steven_offenbacher@unc.edu.
S
S
Offenbacher
D000293:Adolescent; D000328:Adult; D050260:Carbohydrate Metabolism / Q000235:genetics; D002478:Cells, Cultured; D055113:Chronic Periodontitis / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics; D005881:Gingiva / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005891:Gingivitis / Q000235:genetics / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000235:genetics*; D007333:Insulin Resistance / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D017622:Periodontal Attachment Loss / Q000235:genetics / Q000378:metabolism; D010514:Periodontal Pocket / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D055815:Young Adult
D007328:Insulin; D008070:Lipopolysaccharides; D005954:Glucosephosphate Dehydrogenase; D005947:Glucose
carbohydrate metabolism; gene expression; gingiva; gingivitis; inflammation; periodontitis