Malin, Steven K.Kirwan, John P.Sia, Chang LingGonzález, Frank2016-06-132016-06-132014-01Malin, S. K., Kirwan, J. P., Sia, C. L., & González, F. (2014). Glucose-Stimulated Oxidative Stress in Mononuclear Cells Is Related to Pancreatic β-Cell Dysfunction in Polycystic Ovary Syndrome. The Journal of Clinical Endocrinology and Metabolism, 99(1), 322–329. http://doi.org/10.1210/jc.2013-3177https://hdl.handle.net/1805/9932CONTEXT: 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.en-USPublisher PolicyOxidative stressReactive oxygen speciesPancreatic β-cell dysfunctionMononuclear cell (MNC)-derived ROS generationP47phox protein contentArticle