Obesity-associated Gingival Vascular Inflammation and Insulin Resistance

J Dent Res. 2014 Jun;93(6):596-601. doi: 10.1177/0022034514532102. Epub 2014 Apr 17.


Obesity is a risk factor for periodontitis, but the pathogenic mechanism involved is unclear. We studied the effects of insulin in periodontal tissues during the state of obesity-induced insulin resistance. Gingival samples were collected from fatty (ZF) and lean (ZL, control) Zucker rats. Endothelial nitric oxide synthase (eNOS) expression was decreased, and activities of protein kinase C (PKC) α, ß2, δ, and ϵ isoforms were significantly increased in the gingiva from ZF rats compared with those from ZL rats. Expression of oxidative stress markers (mRNA) and the p65 subunit of NF-κB was significantly increased in ZF rats. Immunohistochemistry revealed that NF-κB activation was also increased in the gingival endothelial cells from transgenic mice overexpressing NF-κB-dependent enhanced green fluorescent protein (GFP) and on a high-fat vs. normal chow diet. Analysis of the gingiva showed that insulin-induced phosphorylation of IRS-1, Akt, and eNOS was significantly decreased in ZF rats, but Erk1/2 activation was not affected. General PKC inhibitor and an anti-oxidant normalized the action of insulin on Akt and eNOS activation in the gingiva from ZF rats. This provided the first documentation of obesity-induced insulin resistance in the gingiva. Analysis of our data suggested that PKC activation and oxidative stress may selectively inhibit insulin-induced Akt and eNOS activation, causing endothelial dysfunction and inflammation.

Keywords: NF-kappa B; endothelial nitric oxide synthase; oxidative stress; periodontal bone loss; periodontitis; protein kinase C.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alveolar Bone Loss / etiology
  • Alveolar Bone Loss / metabolism
  • Animals
  • Endothelial Cells / chemistry
  • Endothelium, Vascular / chemistry
  • Gingivitis / etiology*
  • Gingivitis / metabolism
  • Insulin Receptor Substrate Proteins / analysis
  • Insulin Resistance / physiology*
  • Male
  • Mice
  • Mice, Transgenic
  • Nitric Oxide Synthase Type III / analysis
  • Obesity / complications*
  • Oncogene Protein v-akt / analysis
  • Oxidative Stress / physiology
  • Protein Kinase C beta / analysis
  • Protein Kinase C-alpha / analysis
  • Protein Kinase C-delta / analysis
  • Protein Kinase C-epsilon / analysis
  • Rats
  • Rats, Zucker
  • Transcription Factor RelA / analysis
  • Vasculitis / etiology*
  • Vasculitis / metabolism


  • Insulin Receptor Substrate Proteins
  • Irs1 protein, rat
  • Rela protein, rat
  • Transcription Factor RelA
  • Nitric Oxide Synthase Type III
  • Oncogene Protein v-akt
  • Protein Kinase C beta
  • Protein Kinase C-alpha
  • Protein Kinase C-delta
  • Protein Kinase C-epsilon