Hyperglycemia and xerostomia are key determinants of tooth decay in type 1 diabetic mice

Chih-ko Yeh, Stephen E Harris, Sumathy Mohan, Diane Horn, Roberto Fajardo, Yong-hee P Chun, James Jorgensen, Mary MacDougall, Sherry Abboud-Werner

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Insulin-dependent type 1 diabetes mellitus (DM) and oral diseases are closely interrelated. Poor metabolic control in diabetics is associated with a high risk of gingivitis, periodontitis and tooth loss. Salivary flow declines in diabetics and patients suffer from xerostomia. Reduced saliva predisposes to enamel hypomineralization and caries formation; however, the mechanisms that initiate and lead to progression of tooth decay and periodontitis in type 1 DM have not been explored. To address this issue, we analyzed tooth morphology in Akita -/-mice that harbor a point mutation in the Ins2 insulin gene, which leads to progressive hyperglycemia. Mandibles from Akita-/-and wild-type littermates were analyzed by microCT, scanning EM and histology; teeth were examined for amelogenin (Amel) and ameloblastin (Ambn) expression. Mice were injected with pilocarpine to assess saliva production. As hyperglycemia may alter pulp repair, the effect of high glucose levels on the proliferation/ differentiation of cultured MD10-F2 pulp cells was also analyzed. Results showed that Akita -/-mice at 6 weeks of age showed chalky white incisors that correlated with marked hyperglycemia and impaired saliva production. MicroCT of Akita-/-teeth revealed excessive enamel wearing and hypomineralization; immunostaining for Amel and Ambn was decreased. A striking feature was invasion of dentinal tubules with Streptococcus mitis and microabcesses that originated in the coronal pulp and progressed to pulp necrosis and periapical periodontitis. High levels of glucose also inhibited MD10-F2 cell proliferation and differentiation. Our findings provide the first evidence that hyperglycemia in combination with reduced saliva in a model of type1 DM leads to decreased enamel mineralization/matrix proteins and predisposes to excessive wearing and decay. Importantly, hyperglycemia adversely affects enamel matrix proteins and pulp repair. Early detection and treatment of hyperglycemia and hyposalivation may provide a useful strategy for preventing the dental complications of diabetes and promoting oral health in this population.

Original languageEnglish (US)
Pages (from-to)868-882
Number of pages15
JournalLaboratory Investigation
Volume92
Issue number6
DOIs
StatePublished - Jun 2012

Fingerprint

Xerostomia
Hyperglycemia
Tooth
Saliva
Type 1 Diabetes Mellitus
Amelogenin
X-Ray Microtomography
Periodontitis
Dental Enamel
Mouth Diseases
Dental Pulp Necrosis
Streptococcus mitis
Periapical Periodontitis
Glucose
Tooth Loss
Gingivitis
Pilocarpine
Oral Health
Diabetes Complications
Incisor

Keywords

  • diabetes
  • enamel
  • hyperglycemia
  • pulpitis
  • saliva

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Cell Biology
  • Molecular Biology

Cite this

Hyperglycemia and xerostomia are key determinants of tooth decay in type 1 diabetic mice. / Yeh, Chih-ko; Harris, Stephen E; Mohan, Sumathy; Horn, Diane; Fajardo, Roberto; Chun, Yong-hee P; Jorgensen, James; MacDougall, Mary; Abboud-Werner, Sherry.

In: Laboratory Investigation, Vol. 92, No. 6, 06.2012, p. 868-882.

Research output: Contribution to journalArticle

Yeh, C, Harris, SE, Mohan, S, Horn, D, Fajardo, R, Chun, YP, Jorgensen, J, MacDougall, M & Abboud-Werner, S 2012, 'Hyperglycemia and xerostomia are key determinants of tooth decay in type 1 diabetic mice', Laboratory Investigation, vol. 92, no. 6, pp. 868-882. https://doi.org/10.1038/labinvest.2012.60
Yeh, Chih-ko ; Harris, Stephen E ; Mohan, Sumathy ; Horn, Diane ; Fajardo, Roberto ; Chun, Yong-hee P ; Jorgensen, James ; MacDougall, Mary ; Abboud-Werner, Sherry. / Hyperglycemia and xerostomia are key determinants of tooth decay in type 1 diabetic mice. In: Laboratory Investigation. 2012 ; Vol. 92, No. 6. pp. 868-882.
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