title: Increased plasma S100A12 (EN-RAGE) levels in patients with type 2 diabetes.
abstract: S100A12, also called EN-RAGE (extracellular newly identified receptor for advanced glycation end products binding protein) or calcium-binding protein in amniotic fluid-1, is a ligand for RAGE. It has been shown that S100A12 induces adhesion molecules such as vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in the vascular endothelial cell and mediates migration and activation of monocytes/macrophages through RAGE binding and that infusion of lipopolysaccharide into mice causes time-dependent increase of S100A12 in the plasma. Therefore, circulating S100A12 protein may be involved in chronic inflammation in the atherosclerotic lesion. In this study, we developed an ELISA system that uses specific monoclonal antibodies against recombinant human S100A12 to measure plasma S100A12 levels in patients with diabetes. On using our S100A12 ELISA system, the coefficients of variation of intra- and interassay were less than 4 and 9%, respectively. The analytical lower detection limit was 0.2 ng/ml. When plasma S100A12 levels were measured by this system, the concentrations were more than twice as high in the patients with diabetes, compared with those without. Using univariate analysis in all subjects, plasma S100A12 concentrations correlated with hemoglobin A1c, fasting glucose, high-sensitivity C-reactive protein and white blood cell count. Stepwise multiple regression analyses, however, revealed that only white blood cell count and hemoglobin A1c remained significant independent determinants of plasma S100A12 concentration. These results suggest that plasma S100A12 protein levels are regulated by factors related to subclinical inflammation and glucose control in patients with type 2 diabetes.
authors.affiliation: Department of Medicine II, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka 570-8506, Japan. kosakia@takii.kmu.ac.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kosaki
authors.forename: Takamasa
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Tatsuji
authors.initials: T
authors.lastname: Kimura
authors.forename: Kumiko
authors.initials: K
authors.lastname: Iida
authors.forename: Jiro
authors.initials: J
authors.lastname: Hitomi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Matsubara
authors.forename: Yasukiyo
authors.initials: Y
authors.lastname: Mori
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Okigaki
authors.forename: Nagaoki
authors.initials: N
authors.lastname: Toyoda
authors.forename: Hiroya
authors.initials: H
authors.lastname: Masaki
authors.forename: Megumi
authors.initials: M
authors.lastname: Inoue-Shibata
authors.forename: Mitsushige
authors.initials: M
authors.lastname: Nishikawa
authors.forename: Toshiji
authors.initials: T
authors.lastname: Iwasaka
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D009418:S100 Proteins / Q000097:blood*; D000067616:S100A12 Protein
chemical_list: D009418:S100 Proteins; D000067616:S100A12 Protein; C090441:S100A12 protein, human