Reactive oxygen species-induced oxidative stress in the development of insulin resistance and hyperandrogenism in polycystic ovary syndrome

Frank González, Neal S. Rote, Judi Minium, John P. Kirwan

Research output: Contribution to journalArticle

244 Citations (Scopus)

Abstract

Context: Insulin resistance and chronic low level-inflammation are often present in women with polycystic ovary syndrome (PCOS). Objective: The purpose of this study was to determine the effects of hyperglycemia on reactive oxygen species (ROS) generation from mononuclear cells (MNCs) in PCOS. Design: This was a prospective controlled study. Setting: The study was conducted at an academic medical center. Patients: The study population consisted of 16 women with PCOS (eight lean, eight obese) and 15 age- and body composition-matched controls (eight lean, seven obese). Main Outcome Measures: Insulin sensitivity was derived from a 2-h, 75-g oral glucose tolerance test (ISOGTT). ROS generation and p47phox protein expression were quantitated from MNCs obtained from blood drawn fasting and 2 h after glucose ingestion. Results: ISOGTT was lower in PCOS, compared with controls (3.1 ± 0.3 vs. 6.3 ± 0.9, P <0.003). The percent change in ROS generation from MNCs was higher in lean and obese PCOS, compared with lean controls (138.8 ± 21.3 and 154.2 ± 49.1 vs. 0.6 ± 12.7, P <0.003). The percent change in ROS generation from MNCs correlated positively with glucose area under the curve (r = 0.38, P <0.05), and plasma levels of testosterone (r = 0.59, P <0.002) and androstenedione (r = 0.50, P <0.009). The percent change in p47phox from MNCs was also higher in lean and obese PCOS, compared with lean controls (36.2 ± 18.2 and 39.1 ± 8.0 vs. -13.7 ± 8.7, P <0.02); and correlated negatively with IS OGTT (r = -0.39, P <0.05). Conclusion: ROS generation from MNCs in response to hyperglycemia is increased in PCOS independent of obesity. The resultant oxidative stress may contribute to a proinflammatory state that induces insulin resistance and hyperandrogenism in women with this disorder.

Original languageEnglish (US)
Pages (from-to)336-340
Number of pages5
JournalJournal of Clinical Endocrinology and Metabolism
Volume91
Issue number1
DOIs
StatePublished - Jan 2006
Externally publishedYes

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Hyperandrogenism
Oxidative stress
Polycystic Ovary Syndrome
Insulin Resistance
Reactive Oxygen Species
Oxidative Stress
Insulin
Glucose
Glucose Tolerance Test
Hyperglycemia
Androstenedione
Testosterone
Blood
Body Composition
Plasmas
Area Under Curve
Fasting
Blood Cells
Obesity
Eating

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Reactive oxygen species-induced oxidative stress in the development of insulin resistance and hyperandrogenism in polycystic ovary syndrome. / González, Frank; Rote, Neal S.; Minium, Judi; Kirwan, John P.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 91, No. 1, 01.2006, p. 336-340.

Research output: Contribution to journalArticle

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abstract = "Context: Insulin resistance and chronic low level-inflammation are often present in women with polycystic ovary syndrome (PCOS). Objective: The purpose of this study was to determine the effects of hyperglycemia on reactive oxygen species (ROS) generation from mononuclear cells (MNCs) in PCOS. Design: This was a prospective controlled study. Setting: The study was conducted at an academic medical center. Patients: The study population consisted of 16 women with PCOS (eight lean, eight obese) and 15 age- and body composition-matched controls (eight lean, seven obese). Main Outcome Measures: Insulin sensitivity was derived from a 2-h, 75-g oral glucose tolerance test (ISOGTT). ROS generation and p47phox protein expression were quantitated from MNCs obtained from blood drawn fasting and 2 h after glucose ingestion. Results: ISOGTT was lower in PCOS, compared with controls (3.1 ± 0.3 vs. 6.3 ± 0.9, P <0.003). The percent change in ROS generation from MNCs was higher in lean and obese PCOS, compared with lean controls (138.8 ± 21.3 and 154.2 ± 49.1 vs. 0.6 ± 12.7, P <0.003). The percent change in ROS generation from MNCs correlated positively with glucose area under the curve (r = 0.38, P <0.05), and plasma levels of testosterone (r = 0.59, P <0.002) and androstenedione (r = 0.50, P <0.009). The percent change in p47phox from MNCs was also higher in lean and obese PCOS, compared with lean controls (36.2 ± 18.2 and 39.1 ± 8.0 vs. -13.7 ± 8.7, P <0.02); and correlated negatively with IS OGTT (r = -0.39, P <0.05). Conclusion: ROS generation from MNCs in response to hyperglycemia is increased in PCOS independent of obesity. The resultant oxidative stress may contribute to a proinflammatory state that induces insulin resistance and hyperandrogenism in women with this disorder.",
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AU - Rote, Neal S.

AU - Minium, Judi

AU - Kirwan, John P.

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N2 - Context: Insulin resistance and chronic low level-inflammation are often present in women with polycystic ovary syndrome (PCOS). Objective: The purpose of this study was to determine the effects of hyperglycemia on reactive oxygen species (ROS) generation from mononuclear cells (MNCs) in PCOS. Design: This was a prospective controlled study. Setting: The study was conducted at an academic medical center. Patients: The study population consisted of 16 women with PCOS (eight lean, eight obese) and 15 age- and body composition-matched controls (eight lean, seven obese). Main Outcome Measures: Insulin sensitivity was derived from a 2-h, 75-g oral glucose tolerance test (ISOGTT). ROS generation and p47phox protein expression were quantitated from MNCs obtained from blood drawn fasting and 2 h after glucose ingestion. Results: ISOGTT was lower in PCOS, compared with controls (3.1 ± 0.3 vs. 6.3 ± 0.9, P <0.003). The percent change in ROS generation from MNCs was higher in lean and obese PCOS, compared with lean controls (138.8 ± 21.3 and 154.2 ± 49.1 vs. 0.6 ± 12.7, P <0.003). The percent change in ROS generation from MNCs correlated positively with glucose area under the curve (r = 0.38, P <0.05), and plasma levels of testosterone (r = 0.59, P <0.002) and androstenedione (r = 0.50, P <0.009). The percent change in p47phox from MNCs was also higher in lean and obese PCOS, compared with lean controls (36.2 ± 18.2 and 39.1 ± 8.0 vs. -13.7 ± 8.7, P <0.02); and correlated negatively with IS OGTT (r = -0.39, P <0.05). Conclusion: ROS generation from MNCs in response to hyperglycemia is increased in PCOS independent of obesity. The resultant oxidative stress may contribute to a proinflammatory state that induces insulin resistance and hyperandrogenism in women with this disorder.

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