Steven K Malin1, John P Kirwan, Chang Ling Sia, Frank González. 1. 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.
Abstract
CONTEXT: 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). DESIGN: This was a cross-sectional study. SETTING: This study was conducted at an academic medical center. PARTICIPANTS: 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). MAIN OUTCOME VARIABLES: 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. CONCLUSION: 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.
CONTEXT: 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). DESIGN: This was a cross-sectional study. SETTING: This study was conducted at an academic medical center. PARTICIPANTS: 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). MAIN OUTCOME VARIABLES: 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. CONCLUSION: 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: M Ciampelli; A M Fulghesu; F Cucinelli; V Pavone; E Ronsisvalle; M Guido; A Caruso; A Lanzone Journal: Metabolism Date: 1999-02 Impact factor: 8.694
Authors: A Ceriello; N Bortolotti; E Motz; A Crescentini; S Lizzio; A Russo; L Tonutti; C Taboga Journal: Diabetes Care Date: 1998-09 Impact factor: 19.112