Glucose-stimulated oxidative stress in mononuclear cells is related to pancreatic β-cell dysfunction in polycystic ovary syndrome

Steven K. Malin, John P. Kirwan, Chang Ling Sia, Frank González

Research output: Contribution to journalArticle

16 Scopus citations

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 curve 0-30 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. (J Clin Endocrinol Metab 99: 322-329, 2014).

Original languageEnglish (US)
Pages (from-to)322-329
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume99
Issue number1
DOIs
StatePublished - Jan 1 2014

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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