Cited by 337Ovarian function and disordersDiabetes, Cardiovascular Risks, and LipoproteinsMetabolism, Diabetes, and Cancer

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Defects in insulin receptor signaling in vivo in the polycystic ovary syndrome (PCOS)

Dunaif, Andrea, Wu, Xinqi, Lee, Anna, Diamanti-Kandarakis, Evanthia·2001·American Journal of Physiology-Endocrinology and Metabolism

DOI 10.1152/ajpendo.2001.281.2.e392

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Abstract

Women with polycystic ovary syndrome (PCOS) are insulin resistant secondary to a postbinding defect in insulin signaling. Sequential euglycemic glucose clamp studies at 40 and 400 mU · m −2 · min −1 insulin doses with serial skeletal muscle biopsies were performed in PCOS and age-, weight-, and ethnicity-matched control women. Steady-state insulin levels did not differ, but insulin-mediated glucose disposal was significantly decreased in PCOS women ( P < 0.05). Insulin receptor substrate (IRS)-1-associated phosphatidylinositol 3-kinase (PI 3K) activity was significantly decreased in PCOS ( n = 12) compared with control skeletal muscle ( n = 8; P < 0.05). There was no significant difference in the abundance of IR, IRS-1, or the p85 regulatory subunit of PI 3K in PCOS ( n = 14) compared with control ( n = 12) muscle. The abundance of IRS-2 was significantly increased ( P < 0.05) in PCOS skeletal muscle, suggesting a compensatory change. We conclude that there is a physiologically relevant defect in insulin receptor signaling in PCOS that is independent of obesity and type 2 diabetes mellitus.

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Authors: Dunaif, A., Wu, X., Lee, A., & Diamanti-Kandarakis, E.
Affiliations: Brigham and Women's Hospital (US)
Section of Diabetes and Metabolism, Department of Medicine, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033
ORCID: Dunaif, Andrea
Wu, Xinqi
Lee, Anna
Venue: American Journal of Physiology-Endocrinology and Metabolism
Publisher: American Physiological Society
Published: 2001-08-01
Volume: 281
Issue: 2
Pages: E392-E399
ISSN: 0193-1849 (ISSN-L)
1522-1555
DOI: 10.1152/ajpendo.2001.281.2.e392
OpenAlex: W1888335775
Cited by: 337
References: 41
Citations by year: 2026: 7 · 2025: 4 · 2024: 8 · 2023: 12 · 2022: 12 · 2021: 16 · 2020: 10 · 2019: 12 · 2018: 12 · 2017: 9 · 2016: 8 · 2015: 20 · 2014: 19 · 2013: 13 · 2012: 15
FWCI: 11.14
Type: journal article
Language: en
Open access: closed
Locations: American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords: polycystic ovary syndrome, insulin resistance, insulin receptor signaling, IRS-1, insulin receptor substrate 2, phosphatidylinositol 3-kinase, hyperinsulinemic-euglycemic clamp
MeSH terms: Adult, Biopsy, Blood Glucose, Chromatography, Thin Layer, Female, Glucose, Humans, Insulin, Insulin Resistance, Phosphoproteins, Polycystic Ovary Syndrome, Receptor, Insulin, RNA, Messenger, Glucose Clamp Technique, Signal Transduction, Body Mass Index, Muscle, Skeletal, Phosphatidylinositol 3-Kinases, Reverse Transcriptase Polymerase Chain Reaction, Intracellular Signaling Peptides and Proteins, Insulin Receptor Substrate Proteins

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Defects in insulin receptor signaling in vivo in the polycystic ovary syndrome (PCOS)

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