title: Glucose-stimulated oxidative stress in mononuclear cells is related to pancreatic β-cell dysfunction in polycystic ovary syndrome.
abstract: BACKGROUND
  Oxidative stress induced by reactive oxygen species (ROS) is involved in the development of pancreatic β-cell dysfunction.
  
  
  OBJECTIVE
  We determined the relationship between mononuclear cell (MNC)-derived ROS generation and p47phox protein content in response to glucose ingestion and β-cell function in women with polycystic ovary syndrome (PCOS).
  
  
  METHODS
  This was a cross-sectional study.
  
  
  METHODS
  This study was conducted at an academic medical center.
  
  
  METHODS
  Twenty-nine normoglycemic women with PCOS (13 lean, 16 obese) and 25 ovulatory controls (16 lean, 9 obese) underwent a 3-h 75-g oral glucose tolerance test (OGTT).
  
  
  METHODS
  Pancreatic β-cell function was calculated as glucose-stimulated insulin secretion (insulin/glucose area under the curve0-30 min; GSIS)×Matsuda index-derived insulin sensitivity (ISOGTT). ROS generation was measured by chemiluminescence, and p47phox protein was quantified by Western blotting in MNC isolated from blood samples obtained at 0 and 2 hours of the OGTT.
  
  
  RESULTS
  Compared with controls, women with PCOS exhibited a higher percent change from baseline in ROS generation and p47phox protein in conjunction with greater GSIS and a tendency toward lower β-cell function. Lean women with PCOS exhibited a greater percent change from baseline in ROS generation and p47phox protein yet had similar GSIS responses compared with lean controls despite having lower ISOGTT. For the combined groups, β-cell function was inversely related to ROS generation and p47phox protein. GSIS was directly related to body mass index, central obesity, and circulating androgens.
  
  
  CONCLUSIONS
  In normoglycemic women, obesity plays a role in exaggerating GSIS. However, MNC-derived oxidative stress is independent of obesity and may contribute to the decline in β-cell function in women with PCOS.
authors.affiliation: Department of Pathobiology (S.K.M., J.P.K.), Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195; Department of Nutrition (S.K.M., J.P.K.), School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106; and Department of Obstetrics and Gynecology (C.L.S., F.G.), Indiana University School of Medicine, Indianapolis, Indiana 46202.
authors.forename: Steven K
authors.initials: SK
authors.lastname: Malin
authors.forename: John P
authors.initials: JP
authors.lastname: Kirwan
authors.forename: Chang Ling
authors.initials: CL
authors.lastname: Sia
authors.forename: Frank
authors.initials: F
authors.lastname: González
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002478:Cells, Cultured; D003430:Cross-Sectional Studies; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D006801:Humans; D050417:Insulin-Secreting Cells / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D009765:Obesity / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects*; D011085:Polycystic Ovary Syndrome / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology*; D013851:Thinness / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D055815:Young Adult
chemical_list: D005947:Glucose