title: Serum levels of pigment epithelium-derived factor (PEDF) are inversely associated with circulating levels of dipeptidyl peptidase-4 (DPP-4) in humans.
abstract: BACKGROUND
  We have previously found that advanced glycation end products (AGEs) stimulate the proteolytic cleavage of dipeptidyl peptidase-4 (DPP-4) from plasma membranes, and circulating AGE levels are independently correlated with serum DPP-4 values. Since pigment epithelium-derived factor (PEDF), one of the adipocytokines, inhibits the AGEs-induced insulin resistance and vascular damage, it is conceivable that besides AGEs, PEDF might also regulate soluble DPP-4 levels. In this study, we addressed the issue.
  
  
  METHODS
  The study involved 188 subjects (123 males and 65 females; mean age of 61.1±9.2) who visited our hospital for a risk-screening test or treatment for cardiovascular disease. They underwent complete history and physical examinations, and determination of blood chemistry and anthropometric variables, including visceral and subcutaneous fat areas. Serum levels of DPP-4 and PEDF levels were examined by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Median (interquartile range) serum levels of DPP-4 and PEDF were 466.6 (400.2-545.1) ng/mL and 14.0 (10.6-17.0) μg/mL, respectively. Multiple stepwise regression analysis revealed that female (p<0.001), aspartate aminotransferase (p<0.001), glycated hemoglobin (p<0.001) and PEDF (inversely, p=0.020) were independently associated with DPP-4 levels (R(2)=0.267).
  
  
  CONCLUSIONS
  We found here for the first time that serum PEDF levels were one of the independent correlates of circulating DPP-4 levels in humans. Since DPP-4 could impair insulin action and evoke vascular damage, our present study suggests that insulin-sensitizing and atheroprotective properties of PEDF might be ascribed partly to its inhibitory actions on DPP-4.
authors.affiliation: Department of Medicine, Division of Cardio-Vascular Medicine, Kurume University School of Medicine, Kurume, Japan. Electronic address: ntahara@med.kurume-u.ac.jp.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Tahara
authors.affiliation: Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan. Electronic address: shoichi@med.kurume-u.ac.jp.
authors.forename: Sho-Ichi
authors.initials: SI
authors.lastname: Yamagishi
authors.affiliation: Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Matsui
authors.affiliation: Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Nishino
authors.affiliation: Department of Medicine, Division of Cardio-Vascular Medicine, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Honda
authors.affiliation: Department of Medicine, Division of Cardio-Vascular Medicine, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Tahara
authors.affiliation: Department of Medicine, Division of Cardio-Vascular Medicine, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Igata
authors.affiliation: Department of Medicine, Division of Cardio-Vascular Medicine, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fukumoto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000175:diagnosis*; D003430:Cross-Sectional Studies; D018819:Dipeptidyl Peptidase 4 / Q000097:blood*; D005136:Eye Proteins / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000097:blood*; D015843:Serpins / Q000097:blood*; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D015415:Biomarkers; D018819:Dipeptidyl Peptidase 4; D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor; C042807:DPP4 protein, human
keywords: Adipocytokine; Cardiovascular disease; DPP-4; Diabetes; PEDF