Increased activation of nuclear factor κB triggers inflammation and insulin resistance in polycystic ovary syndrome

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

Research output: Contribution to journalArticle

110 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 nuclear factor κB (NFκB) activation and inhibitory κB (IκB) from mononuclear cells (MNC) in PCOS. Design and Setting: This was a prospective controlled study conducted at an academic medical center. Patients: The study population consisted of 16 reproductive-age women with PCOS (eight lean, eight obese) and 16 age- and body composition-matched controls (eight lean, eight obese). Main Outcome Measures: Insulin sensitivity (IS) was derived from a 2-h 75-g oral glucose tolerance test (ISOGTT). Intranuclear NFκB and IκB protein expression were quantitated from MNC obtained from blood drawn fasting and 2 h after glucose ingestion. Results: ISOGTT was lower in PCOS compared with controls (3.3 ± 0.3 vs. 6.4 ± 0.9, P <0.004). The percent change in intranuclear NFκB was higher in lean and obese PCOS compared with lean controls (42.5 ± 19.1 and 54.5 ± 12.5 vs. -14.1 ± 10.9, P <0.006). The percent change in intranuclear NFκB correlated positively with 2-h post-glucose ingestion levels (r = 0.37; P <0.04) and plasma testosterone (r = 0.49; P <0.006) and correlated negatively with ISOGTT (r = 0.39; P <0.04). The percent change in IκB was lower in lean and obese PCOS compared with lean controls (-22.3 ± 3.2 and -17.0 ± 5.0 vs. 8.4 ± 11.8, P <0.02). Conclusion: In response to hyperglycemia, intranuclear NFκB increases and IκB decreases in MNC of women with PCOS independent of obesity. This may represent a cardinal inflammatory signal that contributes to the induction of insulin resistance and hyperandrogenism in PCOS.

Original languageEnglish (US)
Pages (from-to)1508-1512
Number of pages5
JournalJournal of Clinical Endocrinology and Metabolism
Volume91
Issue number4
DOIs
StatePublished - Apr 2006
Externally publishedYes

Fingerprint

Polycystic Ovary Syndrome
Insulin Resistance
Chemical activation
Insulin
Inflammation
Glucose
Hyperglycemia
Testosterone
Blood
Eating
Hyperandrogenism
Plasmas
Glucose Tolerance Test
Body Composition
Chemical analysis
Fasting
Blood Cells
Obesity
Outcome Assessment (Health Care)
Prospective Studies

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Increased activation of nuclear factor κB triggers inflammation and insulin resistance in polycystic ovary syndrome. / González, Frank; Rote, Neal S.; Minium, Judi; Kirwan, John P.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 91, No. 4, 04.2006, p. 1508-1512.

Research output: Contribution to journalArticle

González, Frank ; Rote, Neal S. ; Minium, Judi ; Kirwan, John P. / Increased activation of nuclear factor κB triggers inflammation and insulin resistance in polycystic ovary syndrome. In: Journal of Clinical Endocrinology and Metabolism. 2006 ; Vol. 91, No. 4. pp. 1508-1512.
@article{3e5014c6a0cf46428bdc30af7286a338,
title = "Increased activation of nuclear factor κB triggers inflammation and insulin resistance in polycystic ovary syndrome",
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 nuclear factor κB (NFκB) activation and inhibitory κB (IκB) from mononuclear cells (MNC) in PCOS. Design and Setting: This was a prospective controlled study conducted at an academic medical center. Patients: The study population consisted of 16 reproductive-age women with PCOS (eight lean, eight obese) and 16 age- and body composition-matched controls (eight lean, eight obese). Main Outcome Measures: Insulin sensitivity (IS) was derived from a 2-h 75-g oral glucose tolerance test (ISOGTT). Intranuclear NFκB and IκB protein expression were quantitated from MNC obtained from blood drawn fasting and 2 h after glucose ingestion. Results: ISOGTT was lower in PCOS compared with controls (3.3 ± 0.3 vs. 6.4 ± 0.9, P <0.004). The percent change in intranuclear NFκB was higher in lean and obese PCOS compared with lean controls (42.5 ± 19.1 and 54.5 ± 12.5 vs. -14.1 ± 10.9, P <0.006). The percent change in intranuclear NFκB correlated positively with 2-h post-glucose ingestion levels (r = 0.37; P <0.04) and plasma testosterone (r = 0.49; P <0.006) and correlated negatively with ISOGTT (r = 0.39; P <0.04). The percent change in IκB was lower in lean and obese PCOS compared with lean controls (-22.3 ± 3.2 and -17.0 ± 5.0 vs. 8.4 ± 11.8, P <0.02). Conclusion: In response to hyperglycemia, intranuclear NFκB increases and IκB decreases in MNC of women with PCOS independent of obesity. This may represent a cardinal inflammatory signal that contributes to the induction of insulin resistance and hyperandrogenism in PCOS.",
author = "Frank Gonz{\'a}lez and Rote, {Neal S.} and Judi Minium and Kirwan, {John P.}",
year = "2006",
month = "4",
doi = "10.1210/jc.2005-2327",
language = "English (US)",
volume = "91",
pages = "1508--1512",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "4",

}

TY - JOUR

T1 - Increased activation of nuclear factor κB triggers inflammation and insulin resistance in polycystic ovary syndrome

AU - González, Frank

AU - Rote, Neal S.

AU - Minium, Judi

AU - Kirwan, John P.

PY - 2006/4

Y1 - 2006/4

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 nuclear factor κB (NFκB) activation and inhibitory κB (IκB) from mononuclear cells (MNC) in PCOS. Design and Setting: This was a prospective controlled study conducted at an academic medical center. Patients: The study population consisted of 16 reproductive-age women with PCOS (eight lean, eight obese) and 16 age- and body composition-matched controls (eight lean, eight obese). Main Outcome Measures: Insulin sensitivity (IS) was derived from a 2-h 75-g oral glucose tolerance test (ISOGTT). Intranuclear NFκB and IκB protein expression were quantitated from MNC obtained from blood drawn fasting and 2 h after glucose ingestion. Results: ISOGTT was lower in PCOS compared with controls (3.3 ± 0.3 vs. 6.4 ± 0.9, P <0.004). The percent change in intranuclear NFκB was higher in lean and obese PCOS compared with lean controls (42.5 ± 19.1 and 54.5 ± 12.5 vs. -14.1 ± 10.9, P <0.006). The percent change in intranuclear NFκB correlated positively with 2-h post-glucose ingestion levels (r = 0.37; P <0.04) and plasma testosterone (r = 0.49; P <0.006) and correlated negatively with ISOGTT (r = 0.39; P <0.04). The percent change in IκB was lower in lean and obese PCOS compared with lean controls (-22.3 ± 3.2 and -17.0 ± 5.0 vs. 8.4 ± 11.8, P <0.02). Conclusion: In response to hyperglycemia, intranuclear NFκB increases and IκB decreases in MNC of women with PCOS independent of obesity. This may represent a cardinal inflammatory signal that contributes to the induction of insulin resistance and hyperandrogenism in PCOS.

AB - 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 nuclear factor κB (NFκB) activation and inhibitory κB (IκB) from mononuclear cells (MNC) in PCOS. Design and Setting: This was a prospective controlled study conducted at an academic medical center. Patients: The study population consisted of 16 reproductive-age women with PCOS (eight lean, eight obese) and 16 age- and body composition-matched controls (eight lean, eight obese). Main Outcome Measures: Insulin sensitivity (IS) was derived from a 2-h 75-g oral glucose tolerance test (ISOGTT). Intranuclear NFκB and IκB protein expression were quantitated from MNC obtained from blood drawn fasting and 2 h after glucose ingestion. Results: ISOGTT was lower in PCOS compared with controls (3.3 ± 0.3 vs. 6.4 ± 0.9, P <0.004). The percent change in intranuclear NFκB was higher in lean and obese PCOS compared with lean controls (42.5 ± 19.1 and 54.5 ± 12.5 vs. -14.1 ± 10.9, P <0.006). The percent change in intranuclear NFκB correlated positively with 2-h post-glucose ingestion levels (r = 0.37; P <0.04) and plasma testosterone (r = 0.49; P <0.006) and correlated negatively with ISOGTT (r = 0.39; P <0.04). The percent change in IκB was lower in lean and obese PCOS compared with lean controls (-22.3 ± 3.2 and -17.0 ± 5.0 vs. 8.4 ± 11.8, P <0.02). Conclusion: In response to hyperglycemia, intranuclear NFκB increases and IκB decreases in MNC of women with PCOS independent of obesity. This may represent a cardinal inflammatory signal that contributes to the induction of insulin resistance and hyperandrogenism in PCOS.

UR - http://www.scopus.com/inward/record.url?scp=33646056139&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33646056139&partnerID=8YFLogxK

U2 - 10.1210/jc.2005-2327

DO - 10.1210/jc.2005-2327

M3 - Article

VL - 91

SP - 1508

EP - 1512

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 4

ER -