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J Clin Endocrinol Metab. 2014 Jan;99(1):322-9. doi: 10.1210/jc.2013-3177. Epub 2013 Dec 20.

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

Author information

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.

PMID:
24203060
PMCID:
PMC3879676
DOI:
10.1210/jc.2013-3177
[Indexed for MEDLINE]
Free PMC Article

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