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.
Integrity signals
Registry
Cites
Statistics
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?
Other abnormalities in downstream pathways, such as serine phosphorylation of insulin receptor substrates, inhibit binding with PI3K and prevent propagation of the signal downstream.
“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]
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 2,761 · see citing works
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 · see citing works
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 · see citing works
Self-citationDisruption of IRS-2 causes type 2 diabetes in mice
Withers, D., Gutiérrez, J., Towery, H., Burks, D., Ren, J.-M., Previs, S., Zhang, Y., Bernal, D., Pons, S., Shulman, G., et al. (1998) · Nature · doi:10.1038/36116 · Cited by 1,850 · see citing works
Legro, R. S. (1999) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.84.1.165 · Cited by 1,743 · see citing works
Self-citationKnochenhauer, 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 1,568 · see citing works
Cusi, 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 · see citing works
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 1,067 · see citing works
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 · see citing works
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 917 · see citing works
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× · see citing works
“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 · see citing works
Dunaif, A., Xia, J., Book, C. B., Schenker, E., & Tang, Z. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118126 · Cited by 561 · see citing works
Self-citationDunaif, 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 560 · see citing works
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 · see citing works
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 525 · see citing works
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 520 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 360 · see citing works
Björnholm, M., Kawano, Y., Lehtihet, M., & Zierath, J. R. (1997) · Diabetes · doi:10.2337/diab.46.3.524 · Cited by 358 · see citing works
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 · see citing works
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 · see citing works
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 297 · see citing works
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 · see citing works
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 · see citing works
Fea, K. D., & Roth, R. A. (1997) · Biochemistry · doi:10.1021/bi971157f · Cited by 246 · see citing works
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 · see citing works
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 219 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 121 · see citing works
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 114 · see citing works
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 · see citing works
Modan, M., Harris, M. I., & Halkin, H. (1989) · Diabetes · doi:10.2337/diab.38.12.1630 · Cited by 80 · see citing works
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 · see citing works
Valverde, Á. M., Kahn, C. R., & Benito, M. (1999) · Diabetes · doi:10.2337/diabetes.48.11.2122 · Cited by 53 · see citing works
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 · see citing works
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 · see citing works
Flagged first, then by citations
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 · see citing works
Self-citationDiamanti-Kandarakis, E., & Dunaif, A. (2012) · Endocrine Reviews · doi:10.1210/er.2011-1034 · Cited by 1,947 · see citing works
Self-citationEhrmann, D. A. (2005) · New England Journal of Medicine · doi:10.1056/nejmra041536 · Cited by 1,884 · see citing works
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 · see citing works
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 · see citing works
Dumesic, D. A., Oberfield, S. E., Stener-Victorin, E., Marshall, J. C., Laven, J. S., & Legro, R. S. (2015) · Endocrine Reviews · doi:10.1210/er.2015-1018 · Cited by 1,020 · see citing works
Rojas, J., Chávez-Castillo, M., Olivar, L. C., Rojas, M., Morillo, J., Mejias, J. A., Calvo, M. C. C., & Bermúdez, V. (2014) · International Journal of Reproductive Medicine · doi:10.1155/2014/719050 · Cited by 485 · see citing works
Broekmans, F. J., Knauff, E. A. H., Valkenburg, O., Laven, J. S. E., Eijkemans, M. J. C., & Fauser, B. C. J. M. (2006) · BJOG An International Journal of Obstetrics & Gynaecology · doi:10.1111/j.1471-0528.2006.01008.x · Cited by 445 · see citing works
The Molecular-Genetic Basis of Functional Hyperandrogenism and the Polycystic Ovary Syndrome
Escobar-Morreale, H. F., Luque‐Ramírez, M., & Millán, J. L. S. (2005) · Endocrine Reviews · doi:10.1210/er.2004-0004 · Cited by 420 · see citing works
Zhao, H., Zhang, J., Cheng, X., Nie, X., & He, B. (2023) · Journal of Ovarian Research · doi:10.1186/s13048-022-01091-0 · Cited by 408 · see citing works
Kakoly, N. S., Khomami, M. B., Joham, A. E., Cooray, S. D., Misso, M. L., Norman, R. J., Harrison, C. L., Ranasinha, S., Teede, H. J., & Moran, L. J. (2018) · Human Reproduction Update · doi:10.1093/humupd/dmy007 · Cited by 384 · see citing works
Insulin and hyperandrogenism in women with polycystic ovary syndrome
Baptiste, C. G., Battista, M., Trottier, A., & Baillargeon, J. (2009) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2009.12.010 · Cited by 368 · see citing works
Spritzer, P. M., Lecke, S. B., Satler, F., & Morsch, D. M. (2015) · Reproduction · doi:10.1530/rep-14-0435 · Cited by 330 · see citing works
Molecular mechanisms of insulin resistance in polycystic ovary syndrome
Diamanti-Kandarakis, E., & Papavassiliou, A. G. (2006) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2006.05.006 · Cited by 301 · see citing works
Self-citationPolycystic ovary syndrome: Syndrome XX?
Sam, S., & Dunaif, A. E. (2003) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2003.08.002 · Cited by 302 · see citing works
Self-citationPolycystic ovarian syndrome: Pathophysiology, molecular aspects and clinical implications
Diamanti-Kandarakis, E. (2008) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399408000598 · Cited by 294 · see citing works
Self-citationInsulin-Lowering Agents in the Management of Polycystic Ovary Syndrome
Leo, V. D., Marca, A. L., & Petraglia, F. (2003) · Endocrine Reviews · doi:10.1210/er.2002-0015 · Cited by 289 · see citing works
Chen, Y.-H., Heneidi, S. G., Lee, J.-M., Layman, L. C., Stepp, D. W., Gamboa, G. M., Chen, B.-S., Chazenbalk, G. D., & Azziz, R. (2013) · Diabetes · doi:10.2337/db12-0963 · Cited by 286 · see citing works
Corbould, A., Kim, Y.-B., Youngren, J. F., Pender, C., Kahn, B. B., Lee, A., & Dunaif, A. (2005) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00361.2004 · Cited by 283 · see citing works
Self-citationExercise therapy in polycystic ovary syndrome: a systematic review
Harrison, C. L., Lombard, C. B., Moran, L. J., & Teede, H. J. (2011) · Human Reproduction Update · doi:10.1093/humupd/dmq045 · Cited by 267 · see citing works
Polycystic ovary syndrome current status and future perspective
Naz, R. K. (2014) · Frontiers in Bioscience-Elite · doi:10.2741/e695 · Cited by 267 · see citing works
Sheep models of polycystic ovary syndrome phenotype
Padmanabhan, V., & Veiga‐Lopez, A. (2012) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2012.10.005 · Cited by 222 · see citing works
Skov, V., Glintborg, D., Knudsen, S., Jensen, T. E., Kruse, T. A., Tan, Q., Brusgaard, K., Beck‐Nielsen, H., & Højlund, K. (2007) · Diabetes · doi:10.2337/db07-0275 · Cited by 202 · see citing works
Corbould, A. (2007) · Journal of Endocrinology · doi:10.1677/joe.1.07070 · Cited by 184 · see citing works
Calcaterra, V., Verduci, E., Cena, H., Magenes, V. C., Todisco, C. F., Tenuta, E., Gregorio, C., De Giuseppe, R., Bosetti, A., Di Profio, E., et al. (2021) · Nutrients · doi:10.3390/nu13061848 · Cited by 183 · see citing works
Ollila, M.-M. E., Piltonen, T., Puukka, K., Ruokonen, A., Järvelin, M.-R., Tapanainen, J. S., Franks, S., & Morin-Papunen, L. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-3543 · Cited by 182 · see citing works
Adams, J. M., Taylor, A. E., Crowley, W. F., & Hall, J. E. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031600 · Cited by 179 · see citing works
Increased levels of serum advanced glycation end‐products in women with polycystic ovary syndrome
Diamanti‐Kandarakis, E., Piperi, C., Kalofoutis, A., & Creatsas, G. C. (2004) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2004.02170.x · Cited by 179 · see citing works
Self-citationMetformin administration improves endothelial function in women with polycystic ovary syndrome
Diamanti‐Kandarakis, E., Alexandraki, K., Protogerou, A. D., Piperi, C., Papamichael, C. M., Aessopos, A., Lekakis, J., & Mavrikakis, M. (2005) · European Journal of Endocrinology · doi:10.1530/eje.1.01910 · Cited by 179 · see citing works
Self-citationDiamanti‐Kandarakis, E., Piperi, C., Patsouris, E., Korkolopoulou, P. A., Panidis, D., Pawelczyk, L. A., Papavassiliou, A. G., & Dulęba, A. J. (2007) · Histochemistry and Cell Biology · doi:10.1007/s00418-006-0265-3 · Cited by 176 · see citing works
Self-citationDiamanti‐Kandarakis, E., Katsikis, I., Piperi, C., Kandaraki, E., Piouka, A., Papavassiliou, A. G., & Panidis, D. (2008) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2008.03247.x · Cited by 172 · see citing works
Self-citationDiagnosis, epidemiology, and genetics of the polycystic ovary syndrome
Goodarzi, M. O., & Azziz, R. (2006) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2006.02.005 · Cited by 170 · see citing works
Genetics of polycystic ovary syndrome: searching for the way out of the labyrinth
Diamanti-Kandarakis, E., & Piperi, C. (2005) · Human Reproduction Update · doi:10.1093/humupd/dmi025 · Cited by 167 · see citing works
Self-citationEnhanced Mitogenic Signaling in Skeletal Muscle of Women With Polycystic Ovary Syndrome
Corbould, A. M., Zhao, H., Mirzoeva, S., Aird, F., & Dunaif, A. E. (2006) · Diabetes · doi:10.2337/diabetes.55.03.06.db05-0453 · Cited by 166 · see citing works
Self-citationGenetic rescue of nonclassical ERα signaling normalizes energy balance in obese Erα-null mutant mice
Park, C. J., Zhao, Z., Glidewell-Kenney, C., Lazic, M., Chambon, P., Krust, A., Weiss, J., Clegg, D. J., Dunaif, A., Jameson, J. L., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci41702 · Cited by 162 · see citing works
Self-citationMunir, I., Yen, H.-W., Geller, D. H., Torbati, D., Bierden, R. M., Weitsman, S. R., Agarwal, S. K., & Magoffin, D. A. (2003) · Endocrinology · doi:10.1210/en.2003-0329 · Cited by 163 · see citing works
Polycystic ovary syndrome, adipose tissue and metabolic syndrome
Delitala, A. P., Capobianco, G., Delitala, G., Cherchi, P. L., & Dessole, S. (2017) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-017-4429-2 · Cited by 159 · see citing works
Sending the Signal: Molecular Mechanisms Regulating Glucose Uptake
Krook, A., Wallberg‐Henriksson, H., & Zierath, J. R. (2004) · Medicine & Science in Sports & Exercise · doi:10.1249/01.mss.0000132387.25853.3b · Cited by 150 · see citing works
Selective ovary resistance to insulin signaling in women with polycystic ovary syndrome
Wu, X. K., Zhou, S. Y., Liu, J. X., Pöllänen, P., Sallinen, K., Mäkinen, M., & Erkkola, R. U. (2003) · Fertility and Sterility · doi:10.1016/s0015-0282(03)01007-0 · Cited by 147 · see citing works
Self-citationCorbould, A. (2008) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.872 · Cited by 143 · see citing works
Højlund, K., Glintborg, D., Andersen, N. R., Birk, J. B., Treebak, J. T., Frøsig, C., Beck‐Nielsen, H., & Wojtaszewski, J. F. P. (2007) · Diabetes · doi:10.2337/db07-0706 · Cited by 144 · see citing works
Makker, A., Goel, M. M., Das, V., & Ak, A. (2011) · Gynecological Endocrinology · doi:10.3109/09513590.2011.583955 · Cited by 142 · see citing works
Diamanti‐Kandarakis, E. (2006) · Endocrine · doi:10.1385/endo:30:1:13 · Cited by 136 · see citing works
Self-citationRole of obesity and adiposity in polycystic ovary syndrome
Diamanti‐Kandarakis, E. (2007) · International Journal of Obesity · doi:10.1038/sj.ijo.0803730 · Cited by 129 · see citing works
Self-citationSkeletal Muscle Insulin Resistance in Endocrine Disease
Peppa, Μ., Koliaki, C. C., Nikolopoulos, P., & Raptis, S. (2010) · BioMed Research International · doi:10.1155/2010/527850 · Cited by 129 · see citing works
Polycystic Ovary Syndrome Is Associated with Tissue-Specific Differences in Insulin Resistance
Ciaraldi, T. P., Aroda, V. R., Mudaliar, S. R. D., Chang, R. J., & Henry, R. R. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-1492 · Cited by 128 · see citing works
Implications and Future Perspectives of AGEs in PCOS Pathophysiology
Merhi, Z. O., Kandaraki, E., & Diamanti‐Kandarakis, E. (2019) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2019.01.005 · Cited by 124 · see citing works
Self-citationAdipose Tissue Dysfunction in Polycystic Ovary Syndrome
Bril, F., Ezeh, U., Amiri, M., Hatoum, S., Pace, L., Chen, Y.-H., Bertrand, F., Gower, B., & Azziz, R. (2023) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad356 · Cited by 123 · see citing works
Insulin resistance and polycystic ovary syndrome
Galluzzo, A., Amato, M. C., & Giordano, C. S. D. S. (2008) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2008.05.004 · Cited by 122 · see citing works
Physical activity and mental health in women with Polycystic Ovary Syndrome
Banting, L. K., Gibson-Helm, M., Polman, R., Teede, H. J., & Stepto, N. K. (2014) · BMC Women's Health · doi:10.1186/1472-6874-14-51 · Cited by 121 · see citing works
Hajimonfarednejad, M., Nimrouzi, M., Heydari, M., Zarshenas, M. M., Raee, M. J., & Jahromi, B. N. (2017) · Phytotherapy Research · doi:10.1002/ptr.5970 · Cited by 114 · see citing works
Lorenzo, M. D., Cacciapuoti, N., Lonardo, M. S., Nasti, G., Gautiero, C., Belfiore, A., Guida, B., & Chiurazzi, M. (2023) · Current Nutrition Reports · doi:10.1007/s13668-023-00479-8 · Cited by 129 · see citing works
Indices of low-grade inflammation in polycystic ovary syndrome
DIAMANTI‐KANDARAKIS, E., PATERAKIS, T., & KANDARAKIS, H. A. (2006) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1365.015 · Cited by 112 · see citing works
Self-citationKauffman, R. P., Baker, T. E., Baker, V. M., DiMarino, P., & Castracane, V. D. (2008) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2008.01.037 · Cited by 111 · see citing works
Li, M., YOUNGREN, J. F., Dunaif, A. E., Goldfine, I. D., Maddux, B. A., Zhang, B. B., & Evans, J. L. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-020363 · Cited by 110 · see citing works
Self-citationDiamanti‐Kandarakis, E., Argyrakopoulou, G., Economou, F., Kandaraki, E., & Koutsilieris, M. (2008) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2008.03.014 · Cited by 107 · see citing works
Self-citationCheung, L. P., Ma, R. C. W., Lam, P. M., Lok, I. H., Haines, C. J., So, W. Y., Tong, P. C. Y., Cockram, C. S., Chow, C. C., & Goggins, W. B. (2008) · Human Reproduction · doi:10.1093/humrep/den090 · Cited by 108 · see citing works
DNA methylation in the pathogenesis of polycystic ovary syndrome
Vázquez-Martínez, E. R., Gómez-Viais, Y. I., García-Gómez, E., Reyes-Mayoral, C., Reyes-Muñoz, E., Camacho‐Arroyo, I., & Cerbón, M. A. (2019) · Reproduction · doi:10.1530/rep-18-0449 · Cited by 107 · see citing works
Koistinen, H. A., Chibalin, A., & Zierath, J. R. (2003) · Diabetologia · doi:10.1007/s00125-003-1196-3 · Cited by 107 · see citing works
Tan, S., Scherag, A., Janssen, O. E., Hahn, S., Lahner, H., Dietz, T., Scherag, S., Grallert, H., Vogel, C. I. G., Kimmig, R., et al. (2010) · BMC Medical Genetics · doi:10.1186/1471-2350-11-12 · Cited by 102 · see citing works
Obesity, body composition and metabolic disturbances in polycystic ovary syndrome
Svendsen, P. F., Nilas, L., Nørgaard, K., Jensen, J. B., & Madsbad, S. (2008) · Human Reproduction · doi:10.1093/humrep/den211 · Cited by 103 · see citing works
Ehrmann, D. A., Tang, X. A., Yoshiuchi, I., Cox, N. J., & Bell, G. I. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-020216 · Cited by 99 · see citing works
Nilsson, E., Benrick, A., Kokosar, M., Krook, A., Lindgren, E., Källman, T., Martis, M. M., Højlund, K., Ling, C., & Stener-Victorin, E. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-00935 · Cited by 93 · see citing works
Gonadal soma controls ovarian follicle proliferation through Gsdf in zebrafish
Yan, Y., Desvignes, T., Bremiller, R., WILSON, C. A., Dillon, D. M., High, S. K., Draper, B. W., Buck, C. L., & Postlethwait, J. H. (2017) · Developmental Dynamics · doi:10.1002/dvdy.24579 · Cited by 93 · see citing works
Molecular & genetic factors contributing to insulin resistance in polycystic ovary syndrome.
Mukherjee, S., & Maitra, A. (2010) · PubMed · Cited by 92 · see citing works
Shi, L., Liu, S., Zhao, W., & Shi, J. (2015) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2015.06.023 · Cited by 93 · see citing works
Mechanisms IN endocrinology: metabolic syndrome through the female life cycle
Vryonidou, A., Paschou, S. A., Muscogiuri, G., Orio, F., & Goulis, D. G. (2015) · European Journal of Endocrinology · doi:10.1530/eje-15-0275 · Cited by 88 · see citing works
Józkowiak, M., Piotrowska‐Kempisty, H., Kobylarek, D., Gorska, N., Mozdziak, P. E., Kempisty, B., Rachoń, D., & Spaczyński, R. (2022) · Cells · doi:10.3390/cells12010174 · Cited by 90 · see citing works
Polycystic Ovary Syndrome, Obesity and Reproductive Implications
Hirschberg, A. L. (2009) · Women s Health · doi:10.2217/whe.09.39 · Cited by 83 · see citing works
Johansson, J., Feng, Y., Shao, R., Lönn, M., Billig, H., & Stener‐Victorin, E. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00323.2010 · Cited by 81 · see citing works
Harrison, C. L., Stepto, N. K., Hutchison, S. K., & Teede, H. J. (2012) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2011.04160.x · Cited by 80 · see citing works
Villuendas, G., Botella-Carretero, J. I., Roldán, B., Sancho, J., Escobar-Morreale, H. F., & Millán, J. L. S. (2005) · Human Reproduction · doi:10.1093/humrep/dei205 · Cited by 79 · see citing works
Ovarian Hypertension: Polycystic Ovary Syndrome
Bentley–Lewis, R., Seely, E. W., & Dunaif, A. E. (2011) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2011.01.009 · Cited by 78 · see citing works
Self-citationProteomic analysis of human ovaries from normal and polycystic ovarian syndrome
Ma, X., Fan, L., Meng, Y., Hou, Z., Mao, Y., Wang, W., Ding, W., & Liu, J. (2007) · Molecular Human Reproduction · doi:10.1093/molehr/gam036 · Cited by 78 · see citing works
New biomarkers for diagnosis and management of polycystic ovary syndrome
Karakas, S. E. (2017) · Clinica Chimica Acta · doi:10.1016/j.cca.2017.06.009 · Cited by 81 · see citing works
Long term complications of polycystic ovary syndrome (PCOS)
Peigné, M., & Dewailly, D. (2014) · Annales d Endocrinologie · doi:10.1016/j.ando.2014.07.111 · Cited by 81 · see citing works
Cardiovascular risk in women with polycystic ovary syndrome
Giallauria, F., Orio, F., Palomba, S., Lombardi, G., Colao, A., & Vigorito, C. (2008) · Journal of Cardiovascular Medicine · doi:10.2459/jcm.0b013e32830b58d4 · Cited by 75 · see citing works
Hansen, S., Svendsen, P., Jeppesen, J., Høeg, L. D., Andersen, N. R., Kristensen, J. M., Nilas, L., Lundsgaard, A., Wojtaszewski, J., Madsbad, S., et al. (2018) · Journal of Clinical Endocrinology and Metabolism · doi:10.1210/jc.2018-01771 · Cited by 69 · see citing works
Reyes-Muñoz, E., Sathyapalan, T., Rossetti, P., Shah, M., Long, M., Buscema, M., Valenti, G., Rosa, V. L. L., Cianci, S., & Vitale, S. G. (2018) · Advances in Therapy · doi:10.1007/s12325-018-0810-1 · Cited by 75 · see citing works
González, F., Rote, N. S., Minium, J., & Kirwan, J. P. (2006) · Journal of Endocrinology · doi:10.1677/joe.1.06579 · Cited by 75 · see citing works
Diamanti‐Kandarakis, E., Alexandraki, K., Piperi, C., Aessopos, A., Paterakis, T., Katsikis, I., & Panidis, D. (2006) · Metabolism · doi:10.1016/j.metabol.2006.09.006 · Cited by 75 · see citing works
Self-citationUjvari, D., Hulchiy, M., Calaby, A., Nybacka, A., Bystrom, B., & Hirschberg, A. L. (2014) · Human Reproduction · doi:10.1093/humrep/deu114 · Cited by 72 · see citing works
Penna, I. A. A., Canella, P. R. B., dos Reis, R. M., de Sá, M. F. S., & Ferriani, R. A. (2005) · Human Reproduction · doi:10.1093/humrep/dei104 · Cited by 72 · see citing works
Reappraising the relationship between hyperinsulinemia and insulin resistance in PCOS
Houston, E. J., & Templeman, N. M. (2025) · Journal of Endocrinology · doi:10.1530/joe-24-0269 · Cited by 87 · see citing works
Zierath, J. R., & Wallberg‐Henriksson, H. (2002) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2002.tb04270.x · Cited by 71 · see citing works
Cree‐Green, M., Bergman, B. C., Coe, G. V., Newnes, L., Baumgartner, A., Bacon, S. D., Scherzinger, A. L., Pyle, L. L., & Nadeau, K. J. (2016) · Obesity · doi:10.1002/oby.21651 · Cited by 70 · see citing works
Insulin Metabolism in Polycystic Ovary Syndrome: Secretion, Signaling, and Clearance
Herman, R., Sikonja, J., Jensterle, M., Janez, A., & Dolzan, V. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043140 · Cited by 69 · see citing works
Li, S., Zhai, J., Chu, W., Geng, X., Chen, Z., & Du, Y. (2020) · Translational research · doi:10.1016/j.trsl.2020.02.003 · Cited by 69 · see citing works
Ely, B. R., Clayton, Z. S., McCurdy, C. E., Pfeiffer, J. D., Needham, K. W., Comrada, L. N., & Minson, C. T. (2019) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00549.2018 · Cited by 69 · see citing works
Resistance exercise impacts lean muscle mass in women with polycystic ovary syndrome
KOGURE, G. S., MIRANDA-FURTADO, C. L., SILVA, R. C., MELO, A. S., FERRIANI, R. A., DE SÁ, M. F. S., & REIS, R. M. D. (2016) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000000822 · Cited by 68 · see citing works
Glintborg, D., Hermann, A. P., Andersen, M., Hagen, C., Beck‐Nielsen, H., Veldhuis, J. D., & Henriksen, J. E. (2006) · Fertility and Sterility · doi:10.1016/j.fertnstert.2005.12.067 · Cited by 68 · see citing works
Allemand, M. C., Irving, B. A., Asmann, Y. W., Klaus, K. A., Tatpati, L., Coddington, C. C., & Nair, K. S. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004274 · Cited by 65 · see citing works
Cardiometabolic Risk in PCOS: More than a Reproductive Disorder
Torchen, L. C. (2017) · Current Diabetes Reports · doi:10.1007/s11892-017-0956-2 · Cited by 65 · see citing works
Insulin Signalling and Resistance in Patients with Chronic Heart Failure
Kemppainen, J., Tsuchida, H., Stolen, K. Q., Karlsson, H., Björnholm, M., Heinonen, O. J., Nuutila, P., Krook, A., Knuuti, J. M., & Zierath, J. R. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2003.042648 · Cited by 65 · see citing works
Seow, K., Juan, C., Hsu, Y.-P., Hwang, J., Huang, L., & Ho, L. (2007) · Human Reproduction · doi:10.1093/humrep/del466 · Cited by 64 · see citing works
Nutritional guidelines for the management of insulin resistance
Muscogiuri, G., Barrea, L., Caprio, M., Ceriani, F., Chavez, A. O., El Ghoch, M., Frias-Toral, E., Mehta, R. J., Mendez, V., Paschou, S. A., et al. (2022) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2021.1908223 · Cited by 63 · see citing works
Cardoso, R. C., Puttabyatappa, M., & Padmanabhan, V. (2015) · Neuroendocrinology · doi:10.1159/000381830 · Cited by 62 · see citing works
Luque‐Ramírez, M., Mendieta-Azcona, C., Sánchez, J. M. D. R., Maties, M., & Escobar-Morreale, H. F. (2009) · European Journal of Endocrinology · doi:10.1530/eje-08-0725 · Cited by 62 · see citing works
Cassar, S., Teede, H. J., Harrison, C. L., Joham, A. E., Moran, L., & Stepto, N. K. (2014) · Clinical Endocrinology · doi:10.1111/cen.12619 · Cited by 60 · see citing works
Pertyńska−Marczewska, M., Diamanti‐Kandarakis, E., Zhang, J., & Merhi, Z. O. (2015) · Metabolism · doi:10.1016/j.metabol.2015.08.010 · Cited by 59 · see citing works
Self-citation
- 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
