The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Defects in insulin receptor signaling in vivo in the polycystic ovary syndrome (PCOS)
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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“However, other abnormalities have been observed also in downstream pathways, such as the serine phosphorylation of the insulin receptor substrates which inhibits its binding with PI3K and prevents the propagation of the signal downstream [26, 27].”
From From Prediabetes to Type 2 Diabetes Mellitus in Women with Polycystic Ovary Syndrome: Lifestyle and Pharmacological Management (2020) · cites this paper as [26]
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Sorted by citations
Azziz, R., Carmina, E., Chen, Z., Dunaif, A., Laven, J. S. E., Legro, R. S., Lizneva, D., Natterson-Horowtiz, B., Teede, H. J., & Yildiz, B. O. (2016) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2016.57 · Cited by 2,005
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Polycystic ovary syndrome: etiology, pathogenesis and diagnosis
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Metadata
- 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
- 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
- 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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