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

11 Citations (Scopus)

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

Fingerprint

Oxidative stress
Polycystic Ovary Syndrome
Reactive Oxygen Species
Oxidative Stress
Glucose
Insulin
Proteins
Glucose Tolerance Test
Chemiluminescence
Obesity
Androgens
Abdominal Obesity
Blood
Luminescence
Area Under Curve
Insulin Resistance
Blood Cells
Body Mass Index
Cross-Sectional Studies
Eating

ASJC Scopus subject areas

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

Cite this

Glucose-stimulated oxidative stress in mononuclear cells is related to pancreatic β-cell dysfunction in polycystic ovary syndrome. / Malin, Steven K.; Kirwan, John P.; Sia, Chang Ling; González, Frank.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 99, No. 1, 01.2014, p. 322-329.

Research output: Contribution to journalArticle

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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).",
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