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Periodontitis is more prevalent in patients with T2D than in healthy subjects, and studies indicate that periodontitis impacts the metabolic control of patients with T2D. Hyperglycemia in T2D leads to the formation of advanced glycation end\u2010products (<jats:styled-content style=\"fixed-case\">AGE<\/jats:styled-content>s). Binding of <jats:styled-content style=\"fixed-case\">AGE<\/jats:styled-content>s to the receptor of <jats:styled-content style=\"fixed-case\">AGE<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">RAGE<\/jats:styled-content>) elicits an increased inflammatory response that may be a key modulator linking the two diseases. The present study aimed to elucidate the effect of blocking the <jats:styled-content style=\"fixed-case\">RAGE<\/jats:styled-content> on the interrelationship between <jats:styled-content style=\"fixed-case\">periodontitis<\/jats:styled-content> and T2D in a rat model of both diseases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and methods<\/jats:title><jats:p>Zucker obese rats (HsdHlr:<jats:styled-content style=\"fixed-case\">ZUCKER<\/jats:styled-content>\u2010<jats:italic>Lepr<\/jats:italic> <jats:sup><jats:italic>fa\/fa<\/jats:italic><\/jats:sup>) and their lean littermates were divided into five treatment groups, with and without periodontitis. Monoclonal anti\u2010<jats:styled-content style=\"fixed-case\">RAGE<\/jats:styled-content> IgG<jats:sub>3<\/jats:sub> were injected into the rats three times a week. The diabetic state was evaluated by oral glucose tolerance tests (<jats:styled-content style=\"fixed-case\">OGTTs<\/jats:styled-content>), the homeostasis model assessment (<jats:styled-content style=\"fixed-case\">HOMA<\/jats:styled-content>), concentration of free fatty acids and repeated measurements of blood glucose. Markers of systemic inflammation, including interleukin (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>)\u20101\u03b2, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106 and tumor necrosis factor \u03b1, were evaluated in plasma. Kidney complications were evaluated by quantitative real\u2010time <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>, the creatinine clearance rate, the albumin excretion rate and kidney hypertrophy. Periodontitis was evaluated by morphometric registration of alveolar bone loss and radiographic recording of bone support.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The diabetic state was improved by antibody treatment for 4 wk, resulting in a lower area under the glucose concentration curve during <jats:styled-content style=\"fixed-case\">OGTTs<\/jats:styled-content>, lower insulin levels and a lower <jats:styled-content style=\"fixed-case\">HOMA<\/jats:styled-content>. Furthermore, the antibody treatment resulted in milder kidney complications, as evaluated by measuring the albumin excretion rate and the kidney weight. There was no impact of periodontal inflammation on the level of complications. Periodontal bone support was influenced by diabetes, but the altered diabetic status as a result of treatment with anti\u2010<jats:styled-content style=\"fixed-case\">RAGE<\/jats:styled-content> Ig had no effect on <jats:styled-content style=\"fixed-case\">periodontitis<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In this study, treatment with anti\u2010<jats:styled-content style=\"fixed-case\">RAGE<\/jats:styled-content> IgG<jats:sub>3<\/jats:sub> resulted in improved glucose tolerance and attenuated renal complications. However, no effect was observed on the diabetes\u2010associated <jats:styled-content style=\"fixed-case\">periodontitis<\/jats:styled-content> in Zucker obese rats. Furthermore, <jats:styled-content style=\"fixed-case\">periodontitis<\/jats:styled-content> had no effect on diabetic markers or renal complications. Therefore, activation of <jats:styled-content style=\"fixed-case\">RAGE<\/jats:styled-content> is important in the development of T2D.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jre.12373","type":"journal-article","created":{"date-parts":[[2016,3,14]],"date-time":"2016-03-14T06:33:28Z","timestamp":1457937208000},"page":"97-106","source":"Crossref","is-referenced-by-count":9,"title":["Blockade of <scp>RAGE<\/scp> in Zucker obese rats with experimental periodontitis"],"prefix":"10.1111","volume":"52","author":[{"given":"M. B.","family":"Grauballe","sequence":"first","affiliation":[{"name":"Section for Periodontology Department of Odontology Faculty of Health Aarhus University Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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