Journal
FRONTIERS IN BIOSCIENCE-LANDMARK
Volume 13, Issue -, Pages 1227-1239Publisher
BIOSCIENCE RESEARCH INST-BRI
DOI: 10.2741/2757
Keywords
bacteria; bone; fracture; hyperglycemia; inflammation; infection; microvascular; periodontitis; review
Categories
Funding
- NIAMS NIH HHS [P01 AR49920, P01 AR049920] Funding Source: Medline
- NIDCR NIH HHS [DE07559, R01 DE017732, R01 DE007559, R01 DE017732-02] Funding Source: Medline
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [P01AR049920] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH [R01DE017732] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DENTAL &CRANIOFACIAL RESEARCH [R01DE007559, R23DE007559] Funding Source: NIH RePORTER
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Diabetes mellitus is a metabolic disorder that leads to the development of a number of complications. The etiology of each diabetic complication is undoubtedly multifactorial. We will focus on one potential component that may be common in many diabetic complications, dysregulation of innate immunity associated with an increased inflammatory response. High glucose levels lead to shunting through the polyol pathway, an increase in diacylglycerol which activates protein kinase C, an increase in the release of electrons that react with oxygen molecules to form superoxides, and the non-enzymatic glycosylation of proteins that result in greater formation of advanced glycation end products. Each of these can lead to aberrant cell signalling that affects innate immunity for example, by activating the MAP kinase pathway or inducing activation of transcription factors such as NF-kappaB. This may be a common feature of several complications including periodontal disease, atherosclerosis, nephropathy, impaired healing and retinopathy. These complications are frequently associated with increased expression of inflammatory cytokines such as TNF-alpha, IL-1 beta and IL-6 and enhanced generation of reactive oxygen species. Cause and effect relationship between dysregulation of key components of innate immunity and diabetic complications in many instances have been demonstrated with the use of cytokine blockers and antioxidants.
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