title: Anti-inflammatory role of glucose-dependent insulinotropic polypeptide in periodontitis.
abstract: OBJECTIVE
  The involvement of glucose-dependent insulinotropic polypeptide (GIP) on inflammation was explored in atherosclerosis and adipose tissue. Periodontal disease is a chronic inflammatory disease, and is considered one of the diabetic complications. In the present study, to examine the effect of GIP on periodontitis, we induced experimental periodontitis in glucose-dependent insulinotropic polypeptide receptor-knockout mice (GIPRKO). We also investigated the anti-inflammatory effect of GIP in a culture system.
  
  
  METHODS
  Experimental periodontitis was induced by ligature wire in GIPRKO and C57BL/C mice. Two weeks after the ligature, immunohistological evaluation and inflammatory messenger ribonucleic acid expression in the gingiva was examined. To elucidate the role of GIP in inflammation, the effects of GIP on lipopolysaccharide-induced gene expressions in THP-1 cells were evaluated.
  
  
  RESULTS
  Periodontitis increased inflammatory cell infiltration, macrophage accumulation and tumor necrosis factor-α and nitric oxide synthase gene expressions in the gingiva. Periodontitis in GIPRKO showed a marked increase of inflammatory cells in the gingivomucosal tissue. Mac-1-positive macrophages and the inflammatory gene expressions were significantly increased in periodontitis in GIPRKO compared with C57BL/C mice periodontitis. Immunohistochemical staining confirmed that GIP receptors were expressed in residual and infiltrated Mac-1-positive macrophages. The in vitro study showed that GIP suppressed lipopolysaccharide-induced tumor necrosis factor-α and nitric oxide synthase gene expression in a dose-dependent manner. Furthermore, the inhibitory effect of GIP on lipopolysaccharide-induced inflammatory gene expressions was at least partially through cyclic adenosine monophosphate/protein kinase A pathway.
  
  
  CONCLUSIONS
  These results suggest the beneficial effects of GIP on periodontal disease. In diabetic patients, GIP is expected to have a direct anti-inflammatory effect on periodontitis in addition to its glucose-lowering effect.
authors.affiliation: Department of Periodontology, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Internal Medicine, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Nakamura
authors.affiliation: Department of Internal Medicine, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Miyabe
authors.affiliation: Department of Periodontology, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Nishikawa
authors.affiliation: Department of Periodontology, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Miyajima
authors.affiliation: Department of Periodontology, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Adachi
authors.affiliation: Department of Oral Anatomy, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Mizutani
authors.affiliation: Department of Periodontology, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kikuchi
authors.affiliation: Department of Orthodontics, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Miyazawa
authors.affiliation: Department of Orthodontics, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.
authors.forename: Shigemi
authors.initials: S
authors.lastname: Goto
authors.affiliation: Division of Endocrinology, Diabetes and Geriatric Medicine, Department of Internal Medicine, Akita University School of Medicine, Akita, Japan.
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tsukiyama
authors.affiliation: Division of Endocrinology, Diabetes and Geriatric Medicine, Department of Internal Medicine, Akita University School of Medicine, Akita, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Department of Oral Anatomy, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.
authors.forename: Norikazu
authors.initials: N
authors.lastname: Ohno
authors.affiliation: Department of Periodontology, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.
authors.forename: Toshihide
authors.initials: T
authors.lastname: Noguchi
authors.affiliation: Department of Periodontology, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Mitani
authors.affiliation: Department of Internal Medicine, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.
authors.forename: Tatsuaki
authors.initials: T
authors.lastname: Matsubara
authors.affiliation: Department of Internal Medicine, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Naruse
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010518:Periodontitis / Q000378:metabolism / Q000503:physiopathology*; D011964:Receptors, Gastrointestinal Hormone / Q000235:genetics / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D011964:Receptors, Gastrointestinal Hormone; D014409:Tumor Necrosis Factor-alpha; D005749:Gastric Inhibitory Polypeptide; C041086:gastric inhibitory polypeptide receptor; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse
keywords: Glucose-dependent insulinotropic polypeptide; Inflammation; Periodontal disease