Student or educator? Sign up with your school email and get 6 months of Pro free.
CoChat
Sign Up
Cited by 2,458

The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.

Insulin Resistance and the Polycystic Ovary Syndrome: Mechanism and Implications for Pathogenesis*

Dunaif, Andrea·1997·Endocrine Reviews
DOI 10.1210/edrv.18.6.0318
Open this paper in CoChat — free account

Abstract

It is now clear that PCOS is often associated with profound insulin resistance as well as with defects in insulin secretion. These abnormalities, together with obesity, explain the substantially increased prevalence of glucose intolerance in PCOS. Moreover, since PCOS is an extremely common disorder, PCOS-related insulin resistance is an important cause of NIDDM in women (Table 3). The insulin resistance in at least 50% of PCOS women appears to be related to excessive serine phosphorylation of the insulin receptor. A factor extrinsic to the insulin receptor, presumably a serine/threonine kinase, causes this abnormality and is an example of an important new mechanism for human insulin resistance related to factors controlling insulin receptor signaling. Serine phosphorylation appears to modulate the activity of the key regulatory enzyme of androgen biosynthesis, P450c17. It is thus possible that a single defect produces both the insulin resistance and the hyperandrogenism in some PCOS women (Fig. 19). Recent studies strongly suggest that insulin is acting through its own receptor (rather than the IGF-I receptor) in PCOS to augment not only ovarian and adrenal steroidogenesis but also pituitary LH release. Indeed, the defect in insulin action appears to be selective, affecting glucose metabolism but not cell growth. Since PCOS usually has a menarchal age of onset, this makes it a particularly appropriate disorder in which to examine the ontogeny of defects in carbohydrate metabolism and for ascertaining large three-generation kindreds for positional cloning studies to identify NIDDM genes. Although the presence of lipid abnormalities, dysfibrinolysis, and insulin resistance would be predicted to place PCOS women at high risk for cardiovascular disease, appropriate prospective studies are necessary to directly assess this.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1210/edrv.18.6.0318

Cites

41 of 41 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 41 references

Research works printed but not linked: 233

  1. Dunaif, 1992, Blackwell Scientific
  2. Polson, 1988, Polycystic ovaries — a common finding in normal women., Lancet, 1, 870, 10.1016/S0140-6736(88)91612-1 · DOI · Paper page
  3. Pettersson, 1973, Epidemiology of secondary amenorrhea., Am J Obstet Gynecol, 117, 80, 10.1016/0002-9378(73)90732-1 · DOI
  4. Hull, 1987, Epidemiology of infertility and polycystic ovarian disease: endocrinological and demographic studies., Gynecol Endocrinol, 1, 235, 10.3109/09513598709023610 · DOI · Paper page
  5. Goldzieher, 1962, The polycystic ovary. I. Clinical and histologic features., J Clin Endocrinol Metab, 22, 325, 10.1210/jcem-22-3-325 · DOI · Paper page
  6. Burghen, 1980, Correlation of hyperandrogenism with hyperinsulinism in polycystic ovarian disease., J Clin Endocrinol Metab, 50, 113, 10.1210/jcem-50-1-113 · DOI · Paper page
  7. Dunaif, 1988, Insulin resistance and hyperandrogenism: clinical syndromes and possible mechanisms, In: Pancheri P, Zichella L (eds) Biorhythms and Stress in the Physiopathology of Reproduction. Hemisphere Publishing Co, Washington, DC, pp, 293
  8. Barbieri, 1983, Hyperandrogenism, insulin resistance, and acanthosis nigricans syndrome: a common endocrinopathy with distinct pathophysiologic features., Am J Obstet Gynecol, 147, 90, 10.1016/0002-9378(83)90091-1 · DOI · Paper page
  9. Poretsky, 1987, The gonadotropic function of insulin., Endocr Rev, 8, 132, 10.1210/edrv-8-2-132 · DOI · Paper page
  10. Poretsky, 1991, On the paradox of insulin-induced hyperandrogenism in insulin-resistant states., Endocr Rev, 12, 3, 10.1210/edrv-12-1-3 · DOI · Paper page
  11. Ehrmann, 1995, Polycystic ovary syndrome as a form of functional ovarian hyperandrogenism due to dysregulation of androgen secretion., Endocr Rev, 16, 322, 10.1210/er.16.3.322 · DOI · Paper page
  12. Crowley, 1996, New tools for pituitary-gonadal assessment, In: Filicori M, Flagmini C (eds) The Ovary: Regulation, Dysfunction and Treatment. Elsevier, Amsterdam, pp, 287
  13. Achard, 1921, Le virilisme pilaire et son association a l’insuffisance glycolytique (diabete des femmes a barb)., Bull Acad Natl Med, 86, 51
  14. Kierland, 1947, Acanthosis nigricans: An analysis of data in twenty-two cases and a study of its frequency in necropsy material., J Invest Dermatol, 9, 299, 10.1038/jid.1947.102 · doi:10.1038/jid.1947.102
  15. Brown, 1968, Acanthosis nigricans: a study of 90 cases., Medicine, 47, 33, 10.1097/00005792-196801000-00002 · DOI · Paper page
  16. Barnes, 1974, Insulin resistance, skin changes and virilization: a recessively inherited syndrome possibly due to pineal gland dysfunction., Diabetologia, 10, 284, 10.1007/BF02627729 · DOI
  17. Colle, 1979, Acanthosis nigricans, hirsutisme et diabete insulin-resistant., Arch Fr Pediatr, 36, 518
  18. Taylor, 1992, Mutations in the insulin receptor gene., Endocr Rev, 13, 566, 10.1210/edrv-13-3-566 · DOI · Paper page
  19. Dunaif, 1992, Insulin resistance and ovarian hyperandrogenism., The Endocrinologist, 2, 248, 10.1097/00019616-199207000-00007 · DOI
  20. Kahn, 1976, The syndromes of insulin resistance and acanthosis nigricans., N Engl J Med, 294, 739, 10.1056/NEJM197604012941401 · DOI · Paper page
  21. Flier, 1975, Antibodies that impair insulin receptor binding in an unusual diabetic syndrome with severe insulin resistance., Science, 190, 63, 10.1126/science.170678 · DOI · Paper page
  22. O’Rahilly, 1991, Detection of mutations in insulin-receptor gene in NIDDM patients by analysis of single-stranded conformation polymorphisms., Diabetes, 40, 777, 10.2337/diab.40.6.777 · DOI
  23. Flier, 1985, Acanthosis nigricans in obese women with hyperandrogenism. Characterization of an insulin-resistant state distinct from the Type A and B syndromes., Diabetes, 34, 101, 10.2337/diab.34.2.101 · DOI · Paper page
  24. Dunaif, 1985, The clinical, biochemical and ovarian morphologic features in women with acanthosis nigricans and masculinization., Obstet Gynecol, 66, 545
  25. Stuart, 1986, Insulin resistance with acanthosis nigricans: the roles of obesity and androgen excess., Metabolism, 35, 197, 10.1016/0026-0495(86)90201-5 · DOI
  26. Peters, 1986, Acanthosis nigricans and obesity: acquired and intrinsic defects in insulin action., Metabolism, 35, 807, 10.1016/0026-0495(86)90220-9 · DOI
  27. Pasquali, 1982, Insulin and C-peptide levels in obese patients with polycystic ovaries., Horm Metab Res, 14, 284, 10.1055/s-2007-1018996 · DOI
  28. Shoupe, 1983, Insulin resistance in polycystic ovary syndrome., Am J Obstet Gynecol, 147, 588, 10.1016/0002-9378(83)90023-6 · DOI · Paper page
  29. Chang, 1983, Insulin resistance in nonobese patients with polycystic ovarian disease., J Clin Endocrinol Metab, 57, 356, 10.1210/jcem-57-2-356 · DOI · Paper page
  30. Judd, 1973, Familial hyperthecosis: comparison of endocrinologic and histologic findings with polycystic ovarian disease., Am J Obstet Gynecol, 117, 976, 10.1016/0002-9378(73)90071-9 · DOI
  31. Hughesdon, 1982, Morphology and morphogenesis of the stein-leventhal ovary and of so-called “hyperthecosis.”, Obstet Gynecol Surv, 37, 59, 10.1097/00006254-198202000-00001 · DOI · Paper page
  32. Nagamani, 1986, Hyperinsulinemia in hyperthecosis of the ovaries., Am J Obstet Gynecol, 154, 384, 10.1016/0002-9378(86)90676-9 · DOI
  33. Keettel, 1957, Observations on the PCO syndrome., Am J Obstet Gynecol, 73, 954, 10.1016/S0002-9378(16)37166-6 · DOI
  34. Yen, 1970, Inappropriate secretion of follicle-stimulating hormone and luteinizing hormone in polycystic ovarian disease., J Clin Endocrinol Metab, 30, 435, 10.1210/jcem-30-4-435 · DOI · Paper page
  35. Rebar, 1976, Characterization of the inappropriate gonadotropin secretion in polycystic ovary syndrome., J Clin Invest, 57, 1320, 10.1172/JCI108400 · DOI · Paper page
  36. Waldstreicher, 1988, Hyperfunction of the hypothalamic-pituitary axis in women with polycystic ovarian disease: indirect evidence for partial gonadotroph desensitization., J Clin Endocrinol Metab, 66, 165, 10.1210/jcem-66-1-165 · DOI · Paper page
  37. Dunaif, 1984, The effects of continuous androgen secretion upon the hypothalamic-pituitary-axis in women: evidence from a luteinized thecoma of the ovary., J Clin Endocrinol Metab, 59, 389, 10.1210/jcem-59-3-389 · DOI
  38. Lobo, 1980, Adult manifestation of congenital adrenal hyperplasia due to incomplete 21-hydroxylase deficiency mimicking polycystic ovarian disease., Am J Obstet Gynecol, 138, 720, 10.1016/0002-9378(80)90095-2 · DOI
  39. Ehrmann, 1992, Detection of functional ovarian hyperandrogenism in women with androgen excess., N Engl J Med, 327, 157, 10.1056/NEJM199207163270304 · DOI · Paper page
  40. Yen, 1980, The polycystic ovary syndrome., Clin Endocrinol (Oxf), 12, 177, 10.1111/j.1365-2265.1980.tb02132.x · DOI · Paper page
  41. McKenna, 1983, Amenorrhea with cryptic hyperandrogenemia., J Clin Endocrinol Metab, 56, 893, 10.1210/jcem-56-5-893 · DOI
  42. Mechanick, 1990, Masculinization: a clinical approach to the diagnosis and treatment of hyperandrogenic women, In: Mazzaferri E (ed) Advances in Endocrinology and Metabolism. Mosley Year Book, Inc, Chicago, IL, pp, 129
  43. Futterweit, 1988, The prevalence of hyperandrogenism in 109 consecutive women presenting with diffuse alopecia., J Am Acad Dermatol, 19, 831, 10.1016/S0190-9622(88)70241-8 · DOI
  44. Lobo, 1983, Evidence for the importance of peripheral tissue events in the development of hirsutism in polycystic ovary syndrome., J Clin Endocrinol Metab, 57, 393, 10.1210/jcem-57-2-393 · DOI · Paper page
  45. Dunaif, 1992, Polycystic ovary syndrome and obesity, In: Bjorntorp P, Brodoff BN (eds) Obesity. J.B. Lippincott Co., Philadelphia, pp, 594
  46. Dunaif, 1987, Characterization of groups of hyperandrogenic women with acanthosis nigricans, impaired glucose tolerance and/or hyperinsulinemia., J Clin Endocrinol Metab, 65, 499, 10.1210/jcem-65-3-499 · DOI · Paper page
  47. Dunaif, 1991, Acanthosis nigricans, insulin action, and hyperandrogenism: clinical, histological, and biochemical findings., J Clin Endocrinol Metab, 73, 590, 10.1210/jcem-73-3-590 · DOI
  48. Kahn, 1994, Insulin action, diabetogenes, and the cause of Type II diabetes., Diabetes, 43, 1066, 10.2337/diab.43.8.1066 · DOI · Paper page
  49. Modan, 1989, Evaluation of WHO and NDDG criteria for impaired glucose tolerance., Diabetes, 38, 1603, 10.2337/diab.38.12.1630 · DOI
  50. Dahlgren, 1992, Women with polycystic ovary syndrome wedge resected in 1956 to 1965: a long-term follow-up focusing on natural history and circulating hormones., Fertil Steril, 57, 505, 10.1016/S0015-0282(16)54892-4 · DOI · Paper page
  51. Dunaif, 1989, Profound peripheral insulin resistance, independent of obesity, in the polycystic ovary syndrome., Diabetes, 38, 1165, 10.2337/diab.38.9.1165 · DOI · Paper page
  52. Dunaif, 1992, Evidence for distinctive and intrinsic defects in insulin action in polycystic ovary syndrome., Diabetes, 41, 1257, 10.2337/diab.41.10.1257 · DOI · Paper page
  53. Dunaif, 1993, Ethnicity and polycystic ovary syndrome are associated with independent and additive decreases in insulin action in Caribbean Hispanic women., Diabetes, 42, 1462, 10.2337/diab.42.10.1462 · DOI
  54. Dunaif, 1996, β-Cell dysfunction independent of obesity and glucose intolerance in the polycystic ovary syndrome., J Clin Endocrinol Metab, 81, 942
  55. Apter, 1995, Metabolic features of polycystic ovary syndrome are found in adolescent girls with hyperandrogenism., J Clin Endocrinol Metab, 80, 2966
  56. DeFronzo, 1979, Glucose clamp technique: a method for quantifying insulin secretion and resistance, Am J Physiol, 237, E214
  57. Bergman, 1989, Assessment of insulin sensitivity in vivo: a critical review., Diabetes Metab Rev, 5, 411, 10.1002/dmr.5610050501 · DOI
  58. Yki-Jarvinen, 1983, Effects of body composition on insulin sensitivity., Diabetes, 32, 965, 10.2337/diab.32.10.965 · DOI · Paper page
  59. Bogardus, 1985, Relationship between degree of obesity and in vivo insulin action in man, Am J Physiol, 248, E286
  60. Caro, 1989, Cellular alterations in liver, skeletal muscle, and adipose tissue responsible for insulin resistance in obesity and Type II diabetes., Diabetes Metab Rev, 5, 665, 10.1002/dmr.5610050804 · DOI · Paper page
  61. Kissebah, 1989, Biology of regional body fat distribution: relationship to non-insulin-dependent diabetes mellitus., Diabetes Metab Rev, 5, 83, 10.1002/dmr.5610050202 · DOI · Paper page
  62. Bagatell, 1996, Androgens in men — uses and abuses., N Engl J Med, 334, 707, 10.1056/NEJM199603143341107 · DOI · Paper page
  63. Morales, 1996, Insulin, somatotropic, and luteinizing hormones axes in lean and obese women with polycystic ovary syndrome: common and distinct features., J Clin Endocrinol Metab, 81, 2854
  64. Dunaif, 1995, Hyperandrogenic anovulation (PCOS): a unique disorder of insulin action associated with an increased risk of NIDDM., Am J Med, 98, 33, 10.1016/S0002-9343(99)80057-6 · DOI
  65. Holte, 1994, Enhanced early insulin response to glucose in relation to insulin resistance in women with polycystic ovary syndrome and normal glucose tolerance., J Clin Endocrinol Metab, 78, 1052
  66. O’Meara, 1993, Defects in β-cell function in functional ovarian hyperandrogenism., J Clin Endocrinol Metab, 76, 1241
  67. Weber, 1993, The relation between clinical manifestations of polycystic ovary syndrome and beta-cell function., Clin Endocrinol (Oxf), 38, 295, 10.1111/j.1365-2265.1993.tb01009.x · DOI
  68. Flier, 1982, Impaired in vivo insulin clearance in patients with severe target-cell resistance to insulin., Diabetes, 31, 132, 10.2337/diab.31.2.132 · DOI
  69. Marshall, 1985, Kinetics of insulin receptor internalization and recycling in adipocytes. Shunting of receptors to a degradative pathway by inhibitors of recycling., J Biol Chem, 260, 4136, 10.1016/S0021-9258(18)89242-0 · DOI
  70. Mahabeer, 1989, Insulin and C-peptide secretion in non-obese patients with polycystic ovarian disease., Horm Metab Res, 21, 502, 10.1055/s-2007-1009272 · DOI
  71. Peiris, 1987, Relationship of androgenic activity to splanchnic insulin metabolism and peripheral glucose utilization in premenopausal women., J Clin Endocrinol Metab, 64, 162, 10.1210/jcem-64-1-162 · DOI
  72. Cheatham, 1995, Insulin action and the insulin signaling network., Endocr Rev, 16, 117
  73. Kahn, 1985, The molecular mechanism of insulin action., Annu Rev Med, 36, 429, 10.1146/annurev.me.36.020185.002241 · DOI · Paper page
  74. Kasuga, 1982, The structure of the insulin receptor and its subunits: evidence for multiple non-reduced forms and a 210 kD possible proreceptor., J Biol Chem, 257, 10392, 10.1016/S0021-9258(18)34032-8 · DOI · Paper page
  75. Ullrich, 1985, Human insulin receptor and its relationship to the tyrosine kinase family of oncogenes., Nature, 313, 756, 10.1038/313756a0 · DOI · Paper page
  76. Ebina, 1985, The human insulin receptor cDNA: the structural basis for hormone-activated transmembrane signalling., Cell, 40, 747, 10.1016/0092-8674(85)90334-4 · DOI · Paper page
  77. Kasuga, 1982, Insulin stimulates the phosphorylation of the 95,000-dalton subunit of its own receptor., Science, 215, 185, 10.1126/science.7031900 · DOI · Paper page
  78. Ullrich, 1990, Signal transduction by receptors with tyrosine kinase activity., Cell, 61, 203, 10.1016/0092-8674(90)90801-K · DOI · Paper page
  79. Cantley, 1991, Oncogenes and signal transduction., Cell, 64, 281, 10.1016/0092-8674(91)90639-G · DOI · Paper page
  80. Cobb, 1989, Autophosphorylation activates the soluble cytoplasmic domain of the insulin receptor in an intermolecular reaction., J Biol Chem, 264, 18701, 10.1016/S0021-9258(18)51524-6 · DOI
  81. Shoelson, 1991, Autophosphorylation within insulin receptor β-subunits can occur as an intramolecular process., Biochemistry, 30, 7740, 10.1021/bi00245a010 · DOI
  82. Frattali, 1992, Transmembrane signaling by the human insulin receptor kinase. Relationship between intramolecular β subunit trans- and cis-autophosphorylation and substrate kinase activation., J Biol Chem, 267, 19521, 10.1016/S0021-9258(18)41806-6 · DOI
  83. Myers Jr, 1994, The IRS-1 signaling system., Trends Biochem Sci, 19, 289, 10.1016/0968-0004(94)90007-8 · DOI · Paper page
  84. Sun, 1995, Role of IRS-2 in insulin and cytokine signalling., Nature, 377, 173, 10.1038/377173a0 · DOI · Paper page
  85. Patti, 1995, 4PS/insulin receptor substrate (IRS)-2 is the alternative substrate of the insulin receptor in IRS-1-deficient mice., J Biol Chem, 270, 24670, 10.1074/jbc.270.42.24670 · DOI · Paper page
  86. Sasaoka, 1995, Evidence for a functional role of Shc proteins in mitogenic signaling induced by insulin, insulin-like growth factor-1, and epidermal growth factor., J Biol Chem, 269, 13689, 10.1016/S0021-9258(17)36885-0 · DOI · Paper page
  87. Rose, 1994, Insulin receptor substrate 1 is required for insulin-mediated mitogenic signal transduction., Proc Natl Acad Sci USA, 91, 797, 10.1073/pnas.91.2.797 · DOI
  88. Waters, 1993, Functional expression of insulin receptor substrate-1 is required for insulin-stimulated mitogenic signaling., J Biol Chem, 268, 22231, 10.1016/S0021-9258(18)41513-X · DOI
  89. Okada, 1994, Essential role of phosphatidylinositol 3-kinase in insulin-induced glucose transport and antilipolysis in rat adipocytes., J Biol Chem, 269, 3568, 10.1016/S0021-9258(17)41901-6 · DOI · Paper page
  90. Cheatham, 1994, Phosphatidylinositol 3-kinase activation is required for insulin stimulation of pp70 S6 kinase, DNA synthesis and glucose transporter translocation., Mol Cell Biol, 14, 4902, 10.1128/MCB.14.7.4902 · DOI · Paper page
  91. Kruszynska, 1996, Cellular and molecular mechanisms of non-insulin dependent diabetes mellitus., J Invest Med, 44, 413
  92. Theroux, 1992, Signal transduction by the epidermal growth factor receptor is attenuated by a COOH-terminal domain serine phosphorylation site., J Biol Chem, 267, 16620, 10.1016/S0021-9258(18)42048-0 · DOI
  93. Cochet, 1984, C-kinase phosphorylates the epidermal growth factor receptor and reduces its epidermal growth factor-stimulated tyrosine protein kinase activity., J Biol Chem, 259, 2553, 10.1016/S0021-9258(17)43389-8 · DOI · Paper page
  94. Bollage, 1986, Protein kinase C directly phosphorylates the insulin receptor in vitro and reduces its protein-tyrosine kinase activity., Proc Natl Acad Sci USA, 83, 5822, 10.1073/pnas.83.16.5822 · DOI · Paper page
  95. Takayama, 1988, Phorbol ester-induced serine phosphorylation of the insulin receptor decreases its tyrosine kinase activity., J Biol Chem, 263, 3440, 10.1016/S0021-9258(18)69090-8 · DOI · Paper page
  96. Karasik, 1990, Increased protein kinase C activity is linked to reduced insulin receptor autophosphorylation in liver of starved rats., J Biol Chem, 265, 10226, 10.1016/S0021-9258(18)86935-6 · DOI
  97. Chin, 1994, Activation of protein kinase Cα inhibits insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1., Mol Endocrinol, 8, 51
  98. Muller, 1991, Prevention by protein kinase C inhibitors of glucose-induced insulin-receptor tyrosine kinase resistance in rat fat cells., Diabetes, 40, 1440, 10.2337/diab.40.11.1440 · DOI
  99. Hotamisligil, 1996, IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-α- and obesity-induced insulin resistance., Science, 271, 665, 10.1126/science.271.5249.665 · DOI · Paper page
  100. Boyle, 1991, Phosphopeptide mapping and phosphoamino acid analysis by two-dimensional separation on thin-layer cellulose plates., Methods Enzymol, 201, 110, 10.1016/0076-6879(91)01013-R · DOI · Paper page
  101. Fadden, 1995, Quantitative and selective fluorophore labeling of phosphoserine on peptides and proteins: characterization at the attomole level by capillary electrophoresis and laser-induced fluorescence., Anal Biochem, 225, 81, 10.1006/abio.1995.1111 · doi:10.1006/abio.1995.1111
  102. Jialal, 1987, Evidence for insulin resistance in nonobese patients with polycystic ovarian disease., J Clin Endocrinol Metab, 64, 1066, 10.1210/jcem-64-5-1066 · DOI
  103. Marsden, 1994, Severe impairment of insulin action in adipocytes from amenorrheic subjects with polycystic ovary syndrome., Metabolism, 43, 1536, 10.1016/0026-0495(94)90013-2 · DOI
  104. Ciaraldi, 1997, Cellular insulin resistance in adipocytes from obese polycystic ovary syndrome subjects involves adenosine modulation of insulin sensitivity., J Clin Endocrinol Metab, 82, 1421
  105. Rosenbaum, 1993, Insulin resistance in polycystic ovary syndrome: decreased expression of GLUT-4 glucose transporters in adipocytes, Am J Physiol, 264, E197
  106. Caro, 1991, Clinical Review 26. Insulin resistance in obese and nonobese man., J Clin Endocrinol Metab, 73, 691, 10.1210/jcem-73-4-691 · DOI · Paper page
  107. Freidenberg, 1988, Reversibility of defective adipocyte insulin receptor kinase activity in non-insulin-dependent diabetes mellitus., J Clin Invest, 82, 1398, 10.1172/JCI113744 · DOI · Paper page
  108. Sorbara, 1994, Absence of insulin receptor gene mutations in three women with the polycystic ovary syndrome., Metabolism, 43, 1568, 10.1016/0026-0495(94)90018-3 · DOI
  109. Dunaif, 1997, Diamanti E Defective insulin receptor signaling in vivo in the polycystic ovary syndrome (PCOS)
  110. Talbot, 1996, Molecular scanning of the insulin receptor gene in women with polycystic ovarian syndrome., J Clin Endocrinol Metab, 81, 1979
  111. Lewis, 1990, Threonine 1336 of the human insulin receptor is a major target for phosphorylation by protein kinase C., Biochemistry, 29, 1807, 10.1021/bi00459a020 · DOI
  112. Pillay, 1991, Multisite serine phosphorylation of the insulin and IGF-1 receptors in transfected cells., FEBS Lett, 288, 206, 10.1016/0014-5793(91)81035-7 · DOI
  113. Rapuano, 1991, Phosphorylation of the insulin receptor by a casein kinase I-like enzyme., J Biol Chem, 266, 12902, 10.1016/S0021-9258(18)98780-6 · DOI
  114. Roth, 1987, Phosphorylation of purified insulin receptor by cAMP kinase., Diabetes, 36, 123, 10.2337/diab.36.1.123 · DOI
  115. Stadtmaurer, 1986, Increasing the cAMP content of IM-9 cells alters the phosphorylation state and protein kinase activity of the insulin receptor., J Biol Chem, 261, 3402, 10.1016/S0021-9258(17)35797-6 · DOI · Paper page
  116. Kemp, 1977, Role of multiple basic residues in determining the substrate specificity of cyclic AMP-dependent protein kinase., J Biol Chem, 252, 4888, 10.1016/S0021-9258(17)40137-2 · DOI · Paper page
  117. Guo, 1993, Autophosphorylation-activated protein kinase phosphorylates and inactivates protein phosphatase 2A., Proc Natl Acad Sci USA, 90, 2500, 10.1073/pnas.90.6.2500 · DOI · Paper page
  118. Maddux, 1995, Membrane glycoprotein PC-1 and insulin resistance in non-insulin-dependent diabetes mellitus., Nature, 373, 448, 10.1038/373448a0 · DOI · Paper page
  119. Sbraccia, 1991, Production of inhibitor of insulin-receptor tyrosine kinase in fibroblasts from patient with insulin resistance and NIDDM., Diabetes, 40, 295, 10.2337/diab.40.2.295 · DOI
  120. Jahanfar, 1995, A twin study of polycystic ovary syndrome., Fertil Steril, 63, 478, 10.1016/S0015-0282(16)57412-3 · DOI
  121. Norman, 1996, Hyperinsulinemia is common in family members of women with polycystic ovary syndrome., Fertil Steril, 66, 942, 10.1016/S0015-0282(16)58687-7 · DOI
  122. Ovesen, 1993, Normal basal and insulin-stimulated fuel metabolism in lean women with the polycystic ovary syndrome., J Clin Endocrinol Metab, 77, 1636
  123. Robinson, 1993, The relationship of insulin insensitivity to menstrual pattern in women with hyperandrogenism and polycystic ovaries., Clin Endocrinol (Oxf), 39, 351, 10.1111/j.1365-2265.1993.tb02376.x · DOI · Paper page
  124. Sampson, 1996, Ambulatory blood pressure profiles and plasminogen activator inhibitor (PAI-1) activity in lean women with and without the polycystic ovary syndrome., Clin Endocrinol (Oxf), 45, 623, 10.1046/j.1365-2265.1996.00863.x · DOI · Paper page
  125. Carmina, 1992, Does ethnicity influence the prevalence of adrenal hyperandrogenism and insulin resistance in polycystic ovary syndrome?, Am J Obstet Gynecol, 167, 1807, 10.1016/0002-9378(92)91779-A · DOI · Paper page
  126. Norman, 1995, Ethnic differences in insulin and glucose response to glucose between white and Indian women with polycystic ovary syndrome., Fertil Steril, 63, 58, 10.1016/S0015-0282(16)57297-5 · DOI
  127. Tattersall, 1975, A difference between the inheritance of classical juvenile-onset and maturity-onset type diabetes of young people., Diabetes, 24, 44, 10.2337/diab.24.1.44 · DOI · Paper page
  128. Ghosh, 1996, Genetic analysis of NIDDM. The study of quantitative traits., Diabetes, 45, 1, 10.2337/diab.45.1.1 · DOI
  129. Lillioja, 1987, In vivo insulin action is familial characteristic in nondiabetic Pima indians., Diabetes, 36, 1329, 10.2337/diab.36.11.1329 · DOI · Paper page
  130. Hanis, 1996, A genome-wide search for human non-insulin-dependent (type 2) diabetes genes reveals a major susceptibility locus on chromosome 2., Nat Genet, 13, 161, 10.1038/ng0696-161 · DOI · Paper page
  131. Froguel, 1993, Familial hyperglycemia due to mutations in glucokinase. Definition of a subtype of diabetes mellitus., N Engl J Med, 328, 697, 10.1056/NEJM199303113281005 · DOI · Paper page
  132. Gerbitz, 1996, Mitochondria and diabetes. Genetic, biochemical, and clinical implications of the cellular energy circuit., Diabetes, 45, 113, 10.2337/diab.45.2.113 · DOI · Paper page
  133. Pillay, 1995, The genetics of non-insulin-dependent diabetes mellitus., Adv Genet, 32, 51, 10.1016/S0065-2660(08)60203-5 · DOI
  134. Beck-Nielsen, 1989, Insulin resistance in skeletal muscles of patients with diabetes mellitus., Diabetes Metab Rev, 5, 487, 10.1002/dmr.5610050602 · DOI
  135. Unger, 1995, Lipotoxicity in the pathogenesis of obesity-dependent NIDDM. Genetic and clinical implications., Diabetes, 44, 863, 10.2337/diab.44.8.863 · DOI · Paper page
  136. Wells, 1993, Abnormal activation of glycogen synthesis in fibroblasts from NIDDM subjects., Diabetes, 42, 583, 10.2337/diab.42.4.583 · DOI
  137. Price, 1996, NMR studies of muscle glycogen synthesis in insulin-resistant offspring of parents with non-insulin-dependent diabetes mellitus immediately after glycogen-depleting exercise., Proc Natl Acad Sci USA, 93, 5329, 10.1073/pnas.93.11.5329 · DOI
  138. Cox, 1992, Mapping diabetes-susceptibility genes. Lessons learned from search for DNA marker for maturity-onset diabetes of the young., Diabetes, 41, 401, 10.2337/diab.41.4.401 · DOI
  139. Yki-Jarvinen, 1984, Sex and insulin sensitivity., Metabolism, 33, 1011, 10.1016/0026-0495(84)90229-4 · DOI
  140. Nuutila, 1995, Gender and insulin sensitivity in the heart and in skeletal muscles. Studies using positron emission tomography., Diabetes, 44, 31, 10.2337/diab.44.1.31 · DOI · Paper page
  141. Foley, 1984, Sex differences in insulin-stimulated glucose transport in rat and human adipocytes, Am J Physiol, 246, E211
  142. Moller, 1991, Insulin resistance-mechanisms, syndromes, and implications., N Engl J Med, 325, 938, 10.1056/NEJM199109263251307 · DOI · Paper page
  143. Godsland, 1992, Insulin resistance, secretion, and metabolism in users of oral contraceptives., J Clin Endocrinol Metab, 74, 64
  144. Polderman, 1994, Induction of insulin resistance by androgens and estrogens., J Clin Endocrinol Metab, 79, 265
  145. Holmang, 1992, Effects of short-term testosterone exposure on insulin sensitivity of muscles in female rats, Am J Physiol, 262, E851
  146. Rincon, 1996, Mechanisms behind insulin resistance in rat skeletal muscle after oophorectomy and additional testosterone treatment., Diabetes, 45, 615, 10.2337/diab.45.5.615 · DOI
  147. Dunaif, 1990, Suppression of hyperandrogenism does not improve peripheral or hepatic insulin resistance in the polycystic ovary syndrome., J Clin Endocrinol Metab, 70, 699, 10.1210/jcem-70-3-699 · DOI · Paper page
  148. Diamanti-Kandarakis, 1995, Insulin sensitivity and antiandrogenic therapy in women with polycystic ovary syndrome., Metabolism, 44, 525, 10.1016/0026-0495(95)90062-4 · DOI
  149. Elkind-Hirsch, 1993, Insulin resistance improves in hyperandrogenic women treated with Lupron., Fertil Steril, 60, 634, 10.1016/S0015-0282(16)56213-X · DOI
  150. Moghetti, 1996, The insulin resistance in women with hyperandrogenism is partially reversed by antiandrogen treatment: evidence that androgens impair insulin action in women., J Clin Endocrinol Metab, 81, 952
  151. Marin, 1992, Androgen treatment of middle-aged, obese men: Effects on metabolism, muscle and adipose tissues., Eur J Med, 6, 329
  152. Buffington, 1991, Opposing actions of dehydroepiandrosterone and testosterone on insulin sensitivity., Diabetes, 40, 693, 10.2337/diab.40.6.693 · DOI
  153. Rittmaster, 1993, The role of adrenal hyperandrogenism, insulin resistance, and obesity in the pathogenesis of polycystic ovarian syndrome., J Clin Endocrinol Metab, 76, 1295
  154. Nestler, 1991, Insulin as an effector of human ovarian and adrenal steroid metabolism., Endocrinol Metab Clin North Am, 20, 807, 10.1016/S0889-8529(18)30245-7 · DOI
  155. Diamond, 1985, Human follicular fluid insulin concentrations., J Clin Endocrinol Metab, 61, 990, 10.1210/jcem-61-5-990 · doi:10.1210/jcem-61-5-990
  156. el-Roeiy, 1993, Expression of insulin-like growth factor-I (IGF-I) and IGF-II and the IGF-I, IGF-II, and insulin receptor genes and localization of the gene products in the human ovary., J Clin Endocrinol Metab, 77, 1411
  157. el-Roeiy, 1994, Expression of the genes encoding the insulin-like growth factors (IGF-I and II), the IGF and insulin receptors, and IGF-binding proteins-1–6 and the localization of their gene products in normal and polycystic ovary syndrome ovaries., J Clin Endocrinol Metab, 78, 1488
  158. Czech, 1982, Structural and functional homologies in the receptors for insulin and the insulin-like growth factors., Cell, 31, 8, 10.1016/0092-8674(82)90399-3 · DOI
  159. Froesch, 1985, Insulin-like growth factors and insulin: comparative aspects., Diabetologia, 28, 485, 10.1007/BF00281982 · DOI · Paper page
  160. Leroith, 1995, Molecular and cellular aspects of the insulin-like growth factor I receptor., Endocr Rev, 16, 143, 10.1210/edrv-16-2-143 · DOI · Paper page
  161. Bach, 1995, Insulin-like growth factor binding proteins., Diabetes Rev, 3, 38
  162. Hintz, 1984, IGF-II binding on human lymphoid cells: demonstration of a common high affinity receptor for insulin like peptides., Biochem Biophys Res Commun, 118, 774, 10.1016/0006-291X(84)91462-1 · doi:10.1016/0006-291x(84)91462-1
  163. Jonas, 1989, Delineation of atypical insulin receptors from classical insulin and type I insulin-like growth factor receptors in human placenta., Biochem J, 257, 101, 10.1042/bj2570101 · DOI
  164. Moxham, 1989, Insulin-like growth factor I receptor β-subunit heterogeneity., J Biol Chem, 264, 13238, 10.1016/S0021-9258(18)51620-3 · DOI · Paper page
  165. Moxham, 1992, Insulin/IGF-1 receptor hybrids: a mechanism for increasing receptor diversity., J Cell Biochem, 48, 136, 10.1002/jcb.240480205 · DOI
  166. Erickson, 1995, The ovarian connection, In: Adashi EY, Rock JA, Rosenwaks Z (eds) Reproductive Endocrinology, Surgery, and Technology. Raven Press, New York, pp, 1141
  167. Mason, 1996, Insulin-like growth factor (IGF) I and II, IGF-binding proteins, and IGF-binding protein proteases are produced by theca and stroma of normal and polycystic human ovaries., J Clin Endocrinol Metab, 81, 276
  168. Mason, 1990, Inhibition of oestradiol production by epidermal growth factor in human granulosa cells of normal and polycystic ovaries., Clin Endocrinol (Oxf), 33, 404, 10.1111/j.1365-2265.1990.tb03888.x · DOI
  169. Ballotti, 1989, Intermolecular transphosphorylation between insulin receptors and EGF-insulin receptor chimerae., EMBO J, 8, 3303, 10.1002/j.1460-2075.1989.tb08491.x · DOI
  170. Poretsky, 1988, The effects of experimental hyperinsulinemia on steroid secretion, ovarian insulin receptors, and ovarian type I insulin-like-growth-factor receptors in the rat., Endocrinology, 122, 581, 10.1210/endo-122-2-581 · DOI
  171. Willis, 1995, Insulin action in human granulosa cells from normal and polycystic ovaries is mediated by the insulin receptor and not the Type-I insulin-like growth factor receptor., J Clin Endocrinol Metab, 80, 3788, 10.1210/jcem.80.12.8530637 · doi:10.1210/jcem.80.12.8530637 · Paper page
  172. Dunaif, 1996, Book C-B Selective intrinsic defects in insulin and IGF-1 action in polycystic ovary syndrome (PCOS) in skin fibroblasts
  173. Fox, 1993, Differential effects of oral glucose-mediated vs. intravenous hyperinsulinemia on circulating androgen levels in women., Fertil Steril, 60, 994, 10.1016/S0015-0282(16)56399-7 · DOI
  174. Micic, 1988, Androgen levels during sequential insulin euglycemic clamp studies in patients with polycystic ovary disease., J Steroid Biochem, 31, 995, 10.1016/0022-4731(88)90344-5 · DOI
  175. Prelevic, 1990, Inhibitory effect of sandostatin on secretion of luteinizing hormone, ovarian steroids in polycystic ovary syndrome., Lancet, 336, 900, 10.1016/0140-6736(90)92270-R · DOI
  176. Dunaif, 1996, The insulin sensitizing agent troglitazone: a novel therapy for the polycystic ovary syndrome., J Clin Endocrinol Metab, 81, 3299
  177. Plymate, 1988, Inhibition of sex hormone-binding globulin production in the human hepatoma (Hep G2) cell line by insulin and prolactin., J Clin Endocrinol Metab, 67, 460, 10.1210/jcem-67-3-460 · DOI · Paper page
  178. Gasic, 1997, Urban RJ Troglitazone inhibits progesterone production in porcine granulosa cells
  179. Franks, 1996, Mechanisms of anovulation in polycystic ovary syndrome, In: Filicori M, Flamigni C (eds) The Ovary: Regulation, Dysfunction and Treatment. Elsevier, Amsterdam, pp, 183
  180. Nestler, 1990, Suppression of serum insulin level by diazoxide does not alter serum testosterone or sex hormone-binding globulin levels in healthy, nonobese women., Am J Obstet Gynecol, 163, 1243, 10.1016/0002-9378(90)90698-7 · DOI
  181. Beer, 1994, Disparate effects of insulin reduction with diltiazem on serum dehydroepiandrosterone sulfate levels in obese hypertensive men and women., J Clin Endocrinol Metab, 79, 1077
  182. Moghetti, 1996, Insulin infusion amplifies 17 α-hydroxycorticosteroid intermediates response to adrenocorticotropin in hyperandrogenic women: apparent relative impairment of 17,20-lyase activity., J Clin Endocrinol Metab, 81, 881
  183. Givens, 1971, Familial ovarian hyperthecosis: a study of two families., Am J Obstet Gynecol, 11, 959, 10.1016/0002-9378(71)90550-3 · DOI
  184. Wilroy, 1975, Hyperthecosis — an inheritable form of polycystic ovarian disease., Birth Defects, 11, 81
  185. Givens, 1988, Familial polycystic ovarian disease., Endocrinol Metab Clin North Am, 17, 1, 10.1016/S0889-8529(18)30409-2 · DOI
  186. Ferriman, 1979, The inheritance of polycystic ovarian disease and possible relationship to premature balding., Clin Endocrinol (Oxf), 1, 291, 10.1111/j.1365-2265.1979.tb03077.x · DOI · Paper page
  187. Lunde, 1989, Familial clustering in the polycystic ovarian syndrome., Gynecol Obstet Invest, 28, 23, 10.1159/000293493 · DOI
  188. Mandel, 1983, HLA genotyping in family members and patients with familial polycystic ovarian disease., J Clin Endocrinol Metab, 56, 862, 10.1210/jcem-56-4-862 · DOI
  189. Ober, 1992, Increased risk for polycystic ovary syndrome associated with human leukocyte antigen DQA1*0501., Am J Obstet Gynecol, 167, 1803, 10.1016/0002-9378(92)91778-9 · DOI
  190. Legro, 1995, The genetics of polycystic ovary syndrome., Am J Med, 98, 9, 10.1016/S0002-9343(99)80053-9 · DOI
  191. Rojanasakul, 1985, Tetraploidy in two sisters with the polycystic ovary syndrome., Clin Genet, 27, 167, 10.1111/j.1399-0004.1985.tb00206.x · DOI
  192. Stenchever, 1968, Cytogenic evaluation of 41 patients with Stein-Leventhal syndrome., Obstet Gynecol, 32, 794
  193. Hague, 1988, Familial polycystic ovaries: a genetic disease?, Clin Endocrinol (Oxf), 29, 593, 10.1111/j.1365-2265.1988.tb03707.x · DOI · Paper page
  194. Carey, 1993, Evidence for a single gene effect in polycystic ovaries and male pattern baldness., Clin Endocrinol (Oxf), 38, 653, 10.1111/j.1365-2265.1993.tb02150.x · DOI · Paper page
  195. Gharani, 1997, Association of the steroid synthesis gene CYP11a with polycystic ovary syndrome and hyperandrogenism., Hum Mol Genet, 6, 307, 10.1093/hmg/6.3.397 · DOI · Paper page
  196. Oppenheimer, 1995, Decreased insulin sensitivity in prepubertal girls with premature adrenarche and acanthosis nigricans., J Clin Endocrinol Metab, 80, 614
  197. Conte, 1994, A syndrome of female pseudohermaphroditism, hypergonadotropic hypogonadism, and multicystic ovaries associated with missense mutations in the gene encoding aromatase (P450arom)., J Clin Endocrinol Metab, 78, 1287
  198. Risma, 1995, Targeted overexpression of luteinizing hormone in transgenic mice leads to infertility, polycystic ovaries, and ovarian tumors., Proc Natl Acad Sci USA, 92, 1322, 10.1073/pnas.92.5.1322 · DOI · Paper page
  199. Zhang, 1995, Serine phosphorylation of human P450c17 increases 17,20 lyase activity: implications for adrenarche and the polycystic ovary syndrome., Proc Natl Acad Sci USA, 92, 10619, 10.1073/pnas.92.23.10619 · DOI · Paper page
  200. Carey, 1994, Polycystic ovaries and premature male pattern baldness are associated with one allele of the steroid metabolism gene CYP17., Hum Mol Genet, 3, 1873, 10.1093/hmg/3.10.1873 · DOI · Paper page

200 of 233 shown

Cited by

See all 2,458

Metadata

Authors
Dunaif, A.
Venue
Endocrine Reviews
Publisher
The Endocrine Society
Published
1997-12-01
Volume
18
Issue
6
Pages
774-800
ISSN
  • 0163-769X (ISSN-L)
  • 1945-7189
DOI
10.1210/edrv.18.6.0318
OpenAlex
W2100211815
Cited by
2,458
References
41
FWCI
35.26
Type
journal article
Language
en
Open access
closed

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

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: Insulin Resistance and the Polycystic Ovary Syndrome: Mechanism and Implications for Pathogenesis*. https://app.cochat.ai/papers/10.1210/edrv.18.6.0318
The paper
Dunaif, A. (1997). Insulin Resistance and the Polycystic Ovary Syndrome: Mechanism and Implications for Pathogenesis*. Endocrine Reviews. https://doi.org/10.1210/edrv.18.6.0318

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.