title: Reduction of paraoxonase-1 activity may contribute the qualitative impairment of HDL particles in patients with type 2 diabetes.
abstract: OBJECTIVE
  Cholesterol efflux with high-density lipoprotein (HDL) particles has an important role in the first step of reverse cholesterol transport (RCT). However, HDL function in type 2 diabetes has not been well investigated thoroughly. We measured cholesterol efflux in 36 patients with type 2 diabetes compared with 9 controls without diabetes.
  
  
  METHODS
  The HDL fraction was separated with polyacrylamide gel and recovered using the protein recovery system. Concentration adjusted HDL fraction was used to determine HDL-mediated cholesterol efflux (Efflux-hdl) from THP-1 derived macrophages. We measured paraoxonase-1 (PON 1) activity to determine antioxidation capacity, serum amyloid A protein (SAA) to determine inflammatory response, and carboxymethyl-lysin (CML) to determine antiglucoxidative capacity.
  
  
  RESULTS
  Efflux-hdl demonstrated no correlation with plasma apoprotein A-1 (ApoA-I) or HDL-cholesterol in patients with diabetes. PON1 activity in the patients' HDL fraction was positively correlated with Efflux-hdl (r=0.39, p=0.02), and showed a negative tendency with HbA1c levels (r=-0.28, p=0.10). SAA and CML levels did not demonstrate correlation with Efflux-hdl in patients with diabetes.
  
  
  CONCLUSIONS
  We confirmed the functional changes in HDL particles in the patients. Efflux-hdl from macrophages was reduced depending upon the decrease in PON1 activity, which was inversely related to HbA1c levels.
authors.affiliation: Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, Zaifu-5, Hirosaki Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Murakami
authors.forename: Jutaro
authors.initials: J
authors.lastname: Tanabe
authors.forename: Naoki
authors.initials: N
authors.lastname: Tamasawa
authors.forename: Koki
authors.initials: K
authors.lastname: Matsumura
authors.forename: Maki
authors.initials: M
authors.lastname: Yamashita
authors.forename: Kota
authors.initials: K
authors.lastname: Matsuki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Murakami
authors.forename: Jun
authors.initials: J
authors.lastname: Matsui
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Suda
mesh_terms: D000368:Aged; D016632:Apolipoprotein A-I / Q000097:blood / Q000378:metabolism; D043303:Aryldialkylphosphatase / Q000097:blood*; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism; D001692:Biological Transport; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002460:Cell Line; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000209:etiology / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000097:blood* / Q000302:isolation & purification / Q000378:metabolism; D008239:Lysine / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D000685:Serum Amyloid A Protein / Q000032:analysis / Q000378:metabolism
chemical_list: D016632:Apolipoprotein A-I; D043303:Aryldialkylphosphatase; D015415:Biomarkers; D002784:Cholesterol; D008076:Cholesterol, HDL; D006442:Glycated Hemoglobin; D008075:Lipoproteins, HDL; D008239:Lysine; D000685:Serum Amyloid A Protein; C505693:APOA1 protein, human; C517652:hemoglobin A1c protein, human; C048496:N(6)-carboxymethyllysine; C468406:PON1 protein, human