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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Citations
Cites
Insulin Resistance and the Polycystic Ovary Syndrome: Mechanism and Implications for Pathogenesis
Dunaif, A. E. (1997) · Endocrine Reviews · doi:10.1210/edrv.18.6.0318 · Cited by 2,776
Self-citationHotamisligil, G. S., Peraldi, P., Budavari, A., Ellis, R., White, M. F., & Spiegelman, B. M. (1996) · Science · doi:10.1126/science.271.5249.665 · Cited by 2,630
Profound Peripheral Insulin Resistance, Independent of Obesity, in Polycystic Ovary Syndrome
Dunaif, A., Segal, K. R., Futterweit, W., & Dobrjansky, A. (1989) · Diabetes · doi:10.2337/diab.38.9.1165 · Cited by 1,967
Self-citationDisruption of IRS-2 causes type 2 diabetes in mice
Withers, D. J., Gutierrez, J. S., Towery, H. H., Burks, D. J., Ren, J., Previs, S. F., Zhang, Y., Bernal, D., Pons, S., Shulman, G. I., et al. (1998) · Nature · doi:10.1038/36116 · Cited by 1,775
Knochenhauer, E. S., Key, T. J., Kahsar-Miller, M., Waggoner, W., Boots, L. R., & Azziz, R. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.83.9.5090 · Cited by 1,759
Legro, R. S. (1999) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.84.1.165 · Cited by 1,743
Self-citationCusi, K., Maezono, K., Osman, A., Pendergrass, M., Patti, M. E., Pratipanawatr, T., DeFronzo, R. A., Kahn, C. R., & Mandarino, L. J. (2000) · Journal of Clinical Investigation · doi:10.1172/jci7535 · Cited by 1,139
Cheatham, B., Vlahos, C. J., Cheatham, L. A., Wang, L., Blenis, J., & Kahn, C. R. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.7.4902-4911.1994 · Cited by 1,062
Signaling pathways in insulin action: molecular targets of insulin resistance
Pessin, J. E., & Saltiel, A. R. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10582 · Cited by 939
Okada, T., Kawano, Y., Sakakibara, T., Hazeki, O., & Ui, M. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)41901-6 · Cited by 911
Protein–protein interaction in insulin signaling and the molecular mechanisms of insulin resistance
Virkamäki, A., Ueki, K., & Kahn, C. R. (1999) · Journal of Clinical Investigation · doi:10.1172/jci6609 · Cited by 854 · cited 4×
“Association with the tyrosine-phosphorylated sites on IRS-1/2 results in activation of PI 3K (16, 32, 36, 38).”
BackgroundInfluential(1997) · Diabetes reviews · Cited by 671
Dunaif, A. E., Scott, D., Finegood, D. T., Quintana, B., & Whitcomb, R. W. (1996) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.81.9.8784087 · Cited by 561
Self-citationDunaif, A., Xia, J., Book, C. B., Schenker, E., & Tang, Z. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118126 · Cited by 561
Self-citationEvidence for Distinctive and Intrinsic Defects in Insulin Action in Polycystic Ovary Syndrome
Dunaif, A. E., Segal, K. R., Shelley, D., Green, G., Dobrjansky, A., & Licholai, T. (1992) · Diabetes · doi:10.2337/diab.41.10.1257 · Cited by 544
Self-citationGoodyear, L. J., Giorgino, F., Sherman, L., Carey, J., Smith, R. J., & Dohm, G. L. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117909 · Cited by 527
Suction applied to a muscle biopsy maximizes sample size
Evans, W. J., Phinney, S. D., & Young, V. R. (1982) · Medicine & Science in Sports & Exercise · doi:10.1249/00005768-198201000-00018 · Cited by 525
Tissue-specific insulin resistance in mice with mutations in the insulin receptor, IRS-1, and IRS-2
Kido, Y., Burks, D. J., Withers, D. J., Brüning, J. C., Kahn, C. R., White, M. F., & Accili, D. (2000) · Journal of Clinical Investigation · doi:10.1172/jci7917 · Cited by 491
Kim, Y.-B., Nikoulina, S. E., Ciaraldi, T. P., Henry, R. R., & Kahn, B. B. (1999) · Journal of Clinical Investigation · doi:10.1172/jci6928 · Cited by 487
Krook, A., Björnholm, M., Galuska, D., Jiang, X. J., Fahlman, R., Myers, M. G., Wallberg-Henriksson, H., & Zierath, J. R. (2000) · Diabetes · doi:10.2337/diabetes.49.2.284 · Cited by 375
The IRS-Signaling System: A Network of Docking Proteins That Mediate Insulin and Cytokine Action
White, M. F., & Yenush, L. (1998) · Current topics in microbiology and immunology · doi:10.1007/978-3-642-80481-6_8 · Cited by 362
Björnholm, M., Kawano, Y., Lehtihet, M., & Zierath, J. R. (1997) · Diabetes · doi:10.2337/diab.46.3.524 · Cited by 361
Cellular mechanisms of insulin resistance in polycystic ovarian syndrome
Ciaraldi, T. P. (1992) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.75.2.577 · Cited by 336
Membrane glycoprotein PC-1 and insulin resistance in non-insulin-dependent diabetes mellitus
Maddux, B. A., Sbraccia, P., Kumakura, S., Sasson, S., YOUNGREN, J. F., Fisher, A., Spencer, S. A., Grupe, A., Henzel, W. J., Stewart, T. A., et al. (1995) · Nature · doi:10.1038/373448a0 · Cited by 308
Rondinone, C. M., Wang, L.-M., Lönnroth, P., Wesslau, C., Pierce, J. H., & Smith, U. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.8.4171 · Cited by 295
Kanai, F., Ito, K., Todaka, M., Hayashi, H., Kamohara, S., Ishii, K., Okada, T., Hazeki, O., Ui, M., & Ebina, Y. (1993) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1993.2111 · Cited by 281
Friedman, J. E., Ishizuka, T., Shao, J., Huston, L., Highman, T., & Catalano, P. (1999) · Diabetes · doi:10.2337/diabetes.48.9.1807 · Cited by 255
Fea, K. D., & Roth, R. A. (1997) · Biochemistry · doi:10.1021/bi971157f · Cited by 242
ROSENBAUM, D. S., Haber, R. S., & Dunaif, A. E. (1993) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1993.264.2.e197 · Cited by 223
Self-citationChibalin, A., Yu, M., Ryder, J. W., Song, X. M., Galuska, D., Krook, A., Wallberg‐Henriksson, H., & Zierath, J. R. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.1.38 · Cited by 218
Insulin Signaling in Human Skeletal Muscle: Time Course and Effect of Exercise
Wojtaszewski, J. F. P., Hansen, B. F., Kiens, B., & Richter, E. A. (1997) · Diabetes · doi:10.2337/diab.46.11.1775 · Cited by 206
Selective Insulin Resistance in the Polycystic Ovary Syndrome
Book, C. B., & Dunaif, A. E. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.9.6010 · Cited by 199
Self-citationStructure, regulation and function of phosphoinositide 3-kinases
Fry, M. (1994) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/0925-4439(94)90036-1 · Cited by 182
Walsh, J. P., Caldwell, K. K., & Majerus, P. W. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.20.9184 · Cited by 120
Defect in skeletal muscle phosphatidylinositol-3-kinase in obese insulin-resistant mice.
Heydrick, S. J., Jullien, D., Gautier, N., Tanti, J., Giorgetti‐Peraldi, S., OBBERGHEN, E. V., & MARCHAND‐BRUSTEL, Y. L. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116337 · Cited by 112
Higaki, Y., Wojtaszewski, J. F. P., Hirshman, M. F., Withers, D. J., Towery, H. H., White, M. F., & Goodyear, L. J. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.30.20791 · Cited by 104
Modan, M., Harris, M. I., & Halkin, H. (1989) · Diabetes · doi:10.2337/diab.38.12.1630 · Cited by 80
The Inherent Quantitative Capacity of the Reverse Transcription-Polymerase Chain Reaction
Halford, W. P., Falco, V. C., Gebhardt, B. M., & Carr, D. J. J. (1999) · Analytical Biochemistry · doi:10.1006/abio.1998.2913 · Cited by 77
Valverde, Á. M., Kahn, C. R., & Benito, M. (1999) · Diabetes · doi:10.2337/diabetes.48.11.2122 · Cited by 53
Evaluation of WHO and NDDG criteria for impaired glucose tolerance
Motala, A. A., & Omar, M. A. (1994) · Diabetes Research and Clinical Practice · doi:10.1016/0168-8227(94)90017-5 · Cited by 33
Insulin activation of phosphatidylinositol 3-kinase in human skeletal muscle in vivo
Hickey, M. S., Tanner, C. J., O’Neill, D. S., Morgan, L. J., Dohm, G. L., & Houmard, J. A. (1997) · Journal of Applied Physiology · doi:10.1152/jappl.1997.83.3.718 · Cited by 17
Research works printed but not linked: 10
- Book CB, 1999, J Clin Endocrinol Metab, 84, 3110
- 10.1128/MCB.14.7.4902 · DOI
- Ciaraldi TP, 1992, J Clin Endocrinol Metab, 75, 577
- DeFronzo RA., 1997, Diabetes Rev, 5, 177
- Dunaif A., 1997, Endocr Rev, 18, 774
- Dunaif A, 1996, J Clin Endocrinol Metab, 81, 3299
- Evans WJ, 1982, Med Sci Sports Exerc, 14, 101
- Knochenhauser ES, 1998, J Clin Endocrinol Metab, 83, 3078
- Legro RS, 1999, J Clin Endocrinol Metab, 84, 165
- White MF., 1998, Recent Prog Horm Res, 53, 119
Cited by
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
Self-citationDiamanti-Kandarakis, E., & Dunaif, A. (2012) · Endocrine Reviews · doi:10.1210/er.2011-1034 · Cited by 1,947
Self-citationEhrmann, D. A. (2005) · New England Journal of Medicine · doi:10.1056/nejmra041536 · Cited by 1,920
Polycystic ovary syndrome: etiology, pathogenesis and diagnosis
Goodarzi, M. O., Dumesic, D. A., Chazenbalk, G., & Azziz, R. (2011) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2010.217 · Cited by 1,488
Moran, L. J., Misso, M. L., Wild, R. A., & Norman, R. J. (2010) · Human Reproduction Update · doi:10.1093/humupd/dmq001 · Cited by 1,108
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
