Pancreatic β-cells dysfunction in polycystic ovary syndrome

Panminerva Medica

Volumn 50, Issue 4, 2008, Pages 315-325

  Diamanti Kandarakis, E ^a   Xyrafis, X ^a   Boutzios, G ^a   Christakou, C ^a  

^a UNIVERSITY OF ATHENS MEDICAL SCHOOL   (Greece)

Author keywords

Diabetes mellitus; Insulin resistance; Polycystic ovary syndrome

Indexed keywords

DEXAMETHASONE; DIAGNOSTIC AGENT; INSULIN;

DIABETES MELLITUS; FEMALE; GENETICS; HUMAN; HYPERANDROGENISM; NON INSULIN DEPENDENT DIABETES MELLITUS; OVARY POLYCYSTIC DISEASE; PANCREAS ISLET BETA CELL; PATHOPHYSIOLOGY; PHYSIOLOGY; PREGNANCY; PREGNANCY DIABETES MELLITUS; REVIEW; RISK FACTOR; SECRETION;

DEXAMETHASONE; DIABETES COMPLICATIONS; DIABETES MELLITUS, TYPE 2; DIABETES, GESTATIONAL; FEMALE; HUMANS; HYPERANDROGENISM; INSULIN; INSULIN-SECRETING CELLS; POLYCYSTIC OVARY SYNDROME; PREGNANCY; RISK FACTORS;

EID: 59549097147     PISSN: 00310808     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (85)

1. Diamanti-Kandarakis E, Kouli CR, Bergiele AT, Filandra FA, Tsianateli TC, Spina GG et al. A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile. J Clin Endocrinol Metab 1999;84:4006-11.
2. Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W et al. Androgen Excess Society. Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline. J Clin Endocrinol Metab 2006;91:4237-45.
3. Legro R, Kunselman A, Dodson W, Dunaif A. Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women. J Clin Endocrinol Metab 1999;84:165-9.
4. Ehrmann D, Barnes R, Rosenfield R, Cavaghan M, Imperial J. Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome. Diabetes Care 1999;22:141-6.
5. Gabir MM, Hanson RL, Dabelea D, Imperatore G, Roumain J, Bennett PH et al. The 1997 American Diabetes Association and 1999 World Health Organization criteria for hyperglycemia in the diagnosis and prediction of diabetes. Diabetes Care 2000;23:1108-12
6. Gambineri A, Pelusi C, Manicardi E, Vicennati V, Cacciari M, Morselli-Labate AM et al. Glucose intolerance in a large cohort of Mediterranean women with polycystic ovary syndrome phenotype and associated factors. Diabetes 2004;53:2353-8.
7. Palmert AR, Gordon CM, Kartashov AI, Legro RS, Emans SJ, Dunaif A. Screening for abnormal glucose tolerance in adolescents with polycystic ovary syndrome. J Clin Endocrinol Metab 2002;87:1017-23.
8. Arslanian SA, Lewy VD, Danadian K Glucose intolerance in obese adolescents with polycystic ovary syndrome: roles of insulin resistance and ß-cell dysfunction and risk of cardiovascular disease. J Clin Endocrinol Metab 2001;86:66-71
9. Dunaif A, Graf M, Mandeli J, Laumas V, Dobrjansky A. Characterization of groups of hyperandrogenic women with acanthosis nigricans, impaired glucose tolerance and/or hyperinsulinemia. J Clin Endocrinol Metab 1987;65:499-507.
10. Cibula D, Cifkova R, Fanta M, Poledne R, Zivny J, Skibova J. Increased risk of non-insulin dependent diabetes mellitus, arterial hypertension and coronary artery disease in perimenopausal women with a history of the polycystic ovary syndrome. Hum Reprod 2000;15:785-9.
11. Ehrmann DA, Sturis J, Byrne M, Karrison T, Rosenfield RL, Polonsky K. Insulin secretory defects in polycystic ovary syndrome. Relationship to insulin sensitivity and family history of non-insulin-dependent diabetes mellitus. J Clin Invest 1995;96:520-7.
12. Ciampelli M, Fulgheus AM, Cucinelli F, Pavone V, Caruso A, Mancuso S et al. Heterogeneity in beta cell activity, hepatic insulin clearance and peripheral insulin sensitivity in women with polycystic ovary syndrome. Hum Reprod 1997;12:1897-901.
13. Dunaif A, Diamanti-Kandarakis E, A Lee, X Wu. Defects in insulin receptor signaling in vivo in the polycystic ovary syndrome (PCOS). Am J Physiol Endocrinol Metab 2001;281 E392-9.
14. Corbould A, Kim Y-B, Youngren JF, Pender C, Kahn BB, Lee A et al. Insulin resistance in the skeletal muscle of women with polycystic ovary syndrome involves both intrinsic and acquired defects in insulin signaling. Am J Physiol Endocrinol Metab 2005;288,1047-54.
15. Dunaif A, Segal KR, Futterweit W, Dobrjansky A. Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes 1989;38:1165-74
16. Dunaif A. Insulin action in the polycystic ovary syndrome. Endocrinol Metab Clin North Am 1999;28:341-59
17. Carmina E, Lobo RA Polycystic ovary syndrome (PCOS): arguably the most common endocrinopathy is associated with significant morbidity in women. J Clin Endocrinol Metab 1999;84:1897-9.
18. Dunaif A, Xia, J, Book CB, Schenker E, Tang Z. Excessive insulin receptor serine phosphorylation in cultured fibroblasts and in skeletal muscle. A potential mechanism for insulin resistance. J Clin Invest 1995;96:801-10
19. Bergman RN, Phillips SP, Cobelli C. Physiologic evaluation of factors controlling glucose tolerance in man. J Clin Invest 1981;68:1456-67.
20. Bergman RN. Toward physiological understanding of glucose tolerance. Minimal model approach. Diabetes 1989;38:1512-27.
21. Porte Jr D. Beta cells in type II diabetes mellitus. Diabetes 1991;40:166-80.
22. Dunaif A, Finegood DT. b-Cell dysfunction independent of obesity and glucose intolerance in the polycystic ovary syndrome. J Clin Endocrinol Metab 1996;81:942-7.
23. Holte J, Bergh T, Berne C, Berglund L, Lithell H. 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 1994;78:1052-8.
24. Holte J, Bergh T, Berne C, Lithell H. Restored insulin sensitivity but persistently increased early insulin secretion after weight loss in obese women with polycystic ovary syndrome. J Clin Endocrinol Metab 1995;80:2586-93.
25. Morin-Papunen LC, Vauhkomen I, Koivumen RM, Rouokomen A, Tapanaimen JS. Insulin sensitivity, insulin secretion, and metabolic and hormonal parameters in healthy women and women with polycystic ovary syndrome. Hum Reprod 2000;15:1266-74.
26. Gennarelli G, Rovei V, Novi RF, Holte J, Bongioanni F, Revelli A. Preserved insulin sensitivity and β cell activity, but decreased glucose effectiveness in normal-weight women with the polycystic ovary syndrome. J Clin Endocrinol Metab 2005;90:3381-6.
27. Svendsen PF, Nilas L, Nørgaard K, Jensen JE, Madsbad S. Obesity, body composition and metabolic disturbances in polycystic ovary syndrome. Hum Reprod 2008;23:2113-21.
28. Vrbikova J, Cibula D, Dvorakova K, Stanicka S, Sindelka G, Hill M et al. Insulin sensitivity and ß-cell function in women with polycyslic ovary syndrome. Diabetes Care 2002;25:1217-22.
29. Vrbíkovaø J, Grimmichovaø T, Dvorakova K, Hill M, Stanicka S, Vondra K. Family history of diabetes mellitus determines insulin sensitivity and β cell function in polycystic ovary syndrome. Physiol Res 2008;57:547-53.
30. O'Meara NM, Blackman JD, Ehrmann DA, Barnes RB, Jaspan JB, Rosenfield RL et al. Defects in beta cell function in functional ovarian hyperandrogenism. J Clin Endocrinol Metab 1993b;76:1241-7.
31. Albareda M, Rodriguez-Espinosa J, Murugo M, de Leiva A, Corcoy R. Assessment of insulin sensitivity and beta-cell function from measurements in the fasting state and during an oral glucose tolerance test. Diabetologia 2000;43:1507-11.
32. Goodarzi MO, Erickson S, Port SC, Jennrich RI, Korenman SG. B-cell function: a key pathological determinant in polycystic ovary syndrome. J Clin Endocrinol Metab 2005;90:310-5.
33. Diamanti-Kandarakis E, Panidis D. Unravelling the phenotypic map of polycystic ovary syndrome (PCOS): a prospective study of 634 women with PCOS. Clin Endocrinol (Oxf) 2007;67:735-42.
34. Colilla S, Cox NJ, Ehrmann DA. Heritability of insulin secretion and insulin action in women with polycystic ovary syndrome and their first degree relatives. J Clin Endocrinol Metab 2001;86:2027-31.
35. Henriksen JE, Alford F, Handberg A, Vaag A, Ward GM, Kalfas A et al. Increased glucose effectiveness in normoglycemic but insulin-resistant relatives of patients with non-insulin-dependent diabetes mellitus. J Clin Invest 1994;94:1196-204.
36. Yildiz BO, Yarali H, Oguz H, Bayraktar M. Glucose intolerance, insulin resistance, and hyperandrogenemia in first degree relatives of women with polycystic ovary syndrome. J Clin Endocrinol Metab 2003;88:2031-6.
37. Sam S, Sung Y, Legro R, Dunaif A. Evidence for pancreatic ß-cell dysfunction in brothers of women PCOS. Metabolism 2008;57:84-9.
38. Diamanti-Kandarakis E, Alexandraki K, Bergiele A, Kandarakis H, Mastorakos G, Aessopos A. Presence of metabolic risk factors in non-obese PCOS sisters: evidence of heritability of insulin resistance. J Endocrinol Invest 2004;27:931-6.
39. Sir-Petermann T, Angel B, Maliqueo M, Carvajal F, Santos JL, Perez-Bravo F. Prevalence of type II diabetes mellitus and insulin resistance in parents of women with polycystic ovary syndrome. Diabetologia 2002;45:959-64.
40. Ehrmann DA, Kasza K, Azziz R, Legro RS, Ghazzi MN. Effects of Race and Family History of Type 2 Diabetes on Metabolic Status of Women with Polycystic Ovary Syndrome /Troglitazone. J Clin Endocrinol Metab 2005;90:66-71.
41. Legro RS, Bentley-Lewis R, Driscoll D, Wang SC, Dunaif A. Insulin resistance in the sisters of women with polycystic ovary syndrome: association with hyperandrogenemia rather than menstrual irregularity. J Clin Endocrinol Metab 2002;87:2128-33.
42. Ryan E. Hormones and insulin resistance during pregnancy. Lancet 2003;362:1777-8
43. Barros RP, Morani A, Moriscot A, Machado UF. Insulin resistance of pregnancy involves estrogen-induced repression of muscle GLUT4. Mol Cell Endocrinol 2008 Jul 23. [Epub ahead of print].
44. Catalane PM, Hoegh M, Minium J, Huston-Presley L, Bernard S, Kalhan S et al. Adiponectin in human pregnancy: implications for regulation of glucose and lipid metabolism. Diabetologia 2006;49:1677-85.
45. McLachlan KA, O'Neal D, Jenkins A, Alford FP. Do adiponectin, TNFalpha, leptin and CRP relate to insulin resistance in pregnancy? Studies in women with and without gestational diabetes, during and after pregnancy. Diabetes Metab Res Rev 2006;22:131-8.
46. Retnakaran R, Connelly PW, Maguire G, Sermer M, Zinman B, Hanley AJ. Decreased high-molecular-weight adiponectin in gestational diabetes: implications for the pathophysiology of Type 2 diabetes. Diabet Med 2007;24:245-52.
47. Nien JK, Mazaki-Tovi S, Romero R, Kusanovic JP, Erez O, Gotsch F et al. Resistin: a hormone which induces insulin resistance is increased in normal pregnancy J Perinat Med 2007;35:513-21
48. Devlieger R, Casteels K, Van Assche FA. Reduced adaptation of the pancreatic B cells during pregnancy is the major causal factor for gestational diabetes: Current knowledge and metabolic effects on the offspring Acta Obstet Gynecol Scand 2008;10:1-5.
49. Shaat N, Groop L. Genetics of gestational diabetes mellitus. Curr Med Chem 2007;14:569-83.
50. Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev 1997;18:774-800. Review
51. Diamanti-Kandarakis E. Polycystic ovarian syndrome: pathophysiology, molecular aspects and clinical implications. Expert Rev Mol Med 2008;30;10:e3. Review
52. Siassakos D, Wardle P. Polycystic ovary syndrome and pregnancy outcome: red herring or red flag? BJOG 2007;114:922-32
53. Kashanian M, Fazy Z, Pirak A. Evaluation of the relationship between gestational diabetes and a history of polycystic ovarian syndrome Diabetes Res Clin Pract 2008;80:289-92.
54. Lo JC, Feigenbaum SL, Escobar GJ, Yang J, Crites YM, Ferrara A. Increased prevalence of gestational diabetes mellitus among women with diagnosed polycystic ovary syndrome: a population-based study. Diabetes Care 2006;29:1915-7
55. Wijeyaratne CN, Waduge R, Arandara D, Arasalingam A, Sivasuriam A, Dodampahala SH et al. Metabolic and polycystic ovary syndromes in indigenous South Asian women with previous gestational diabetes mellitus. BJOG 2006;113:1182-7
56. Boomsrna CM, Eijkemans MJ, Hughes EG, Visser GH, Fauser BC, Macklon NS. A meta-analysis of pregnancy outcomes in women with polycystic ovary syndrome Hum Reprod Update 2006;12:673-83
57. Toulis KA, Goulis DG, Kolibianakis EM, Venetis CA, Tarlatzis BC, Papadimas I. Risk of gestational diabetes mellitus in women with polycystic ovary syndrome: a systematic review and a meta-analysisFertil Steril 2008 Aug 16. [Epub ahead of print]
58. Lanzone A, Fulghesu AM, Cucinelli F, Guido M, Pavone V, Caruso A et al. Preconceptional and gestational evaluation of insulin secretion in patients with polycystic ovary syndromeHum Reprod 1996;11:2382-6.
59. Glueck CJ, Pranikoff J, Aregawi D, Wang P. Prevention of gestational diabetes by metformin plus diet in patients with polycystic ovary syndrome. Fertil Steril 2008;89:625-34.
60. Glueck CJ, Goldenberg N, Sieve L, Wang P. An observational study of reduction of insulin resistance and prevention of development of type 2 diabetes mellitus in women with polycystic ovary syndrome treated with metformin and diet. Metabolism 2008;57:954-60.
61. Yogev Y, Visser GH. Obesity, gestational diabetes and pregnancy outcome Semin Fetal Neonatal Med. 2008 Oct 14. [Epub ahead of print],
62. Andrews RC, Walker BR. Glucocorticoids and insulin resistance: old hormones, new targets. Clin Sci 1999;96:513-23.
63. Ogawa A, Johnson JH, Ohneda M, McAllister CT, Inman L, Alam T et al. Roles of insulin resistance and ß-cell dysfunction in dexamethasone-induced diabetes. J Clin Invest 1992;90:497-504.
64. Bonner-Weir S, Trent DF, Zamachinski CJ, Clore ET, Weir GC. Limited beta cell regeneration in a beta cell deficient rat model: studies with dexamethasone. Metabolism 1981;9:914-8.
65. Novelli M, De Tata V, Bombara M, Lorenzini A, Masini M, Pollera M et al. Insufficient adaptative capability of pancreatic endocrine function in dexamethasone-treated ageing rats. J Endocrinol. 1999;162:425-32.
66. Nicod N, Giusti V, Besse C, Tappy L. Metabolic adaptations to dexamethasone-induced insulin resistance in healthy volunteers. Obes Res 2003;11:625-31.
67. Wajngot A, Giacca A, Grill V, Vranic M, Efendic S. The diabetogenic effects of glucocorticoids are more pronounced in low- than in high-insulin responders. Proc Natl Acad Sci USA 1992;89:6035-9.
68. Ehrmann DA, Breda E, Corcoran MC, Cavaghan MK, Imperial J, Toffolo G et al. Impaired beta-cell compensation to dexamethasone-induced hyperglycemia in women with polycystic ovary syndrome. Am J Physiol Endocrinol Metab 2004;287:E241-6.
69. Nelson VL, Legro RS, Strauss JF 3rd, McAllister JM. Augmented androgen production is a stable steroidogenic phenotype of propagated theca cells from polycystic ovaries. Mol Endocrinol 1999;13:946-57.
70. Nestler JE, Jakubowicz DJ, de Vargas AF, Brik C, Quintero N, Medina F. Insulin stimulates testosterone biosynthesis by human thecal cells from women with polycystic ovary syndrome by activating its own receptor and using inositolglycan mediators as the signal transduction system. J Clin Endocrinol Metab 1998;83:2001-5.
71. Poretsky L. Commentary: Polycystic ovary syndrome-increased or preserved ovarian sensitivity to insulin? J Clin Endocrinol Metab 2006;91:2859-60.
72. Baillargeon JR, Carpentier A. Role of insulin in the hyperandrogenemia of lean women with polycystic ovary syndrome and normal insulin sensitivity. Fertil Steril 2007;88:886-93.
73. Polderman KH, Gooren LJ, Asscheman H, Bakker A, Heine RJ. Induction of insulin resistance by androgens and estrogens. J Clin Endocrinol Metab 1994;79:265-71.
74. Elbers JM, Giltay EJ, Teerlink T, Scheffer PG, Asscheman H, Seidell JC et al. Effects of sex steroids on components of the insulin resistance syndrome in transsexual subjects. Clin Endocrinol (Oxf) 2003;58:562-71.
75. Seow KM, Juan CC, Hsu YP, Hwang JL, Huang LW, Ho LT. Amelioration of insulin resistance in women with PCOS via reduced insulin receptor substrate-1 Ser312 phosphorylation following laparoscopic ovarian electrocautery. Hum Reprod 2007;22:1003-10.
76. Eisner JR, Dumesic DA, Kemnitz JW, Abbott DH Timing of prenatal androgen excess determines differential impairment in insulin secretion and action in adult female rhesus monkeys. J Clin Endocrinol Metab 2000;85:1206-10.
77. Nilsson C, Niklasson M, Eriksson E, Bjorntorp P, Holmang A. Imprinting of female offspring with testosterone results in insulin resistance and changes in body fat distribution at adult age in rats. J Clin Invest 1998:101:74-8.
78. Mannerǎs L, Cajander S, Holmäng A, Seleskovic Z, Lystig T, Lönn M et al. A new rat model exhibiting both ovarian and metabolic characteristics of polycystic ovary syndrome. Endocrinology 2007;148:3781-91.
79. Allemand M, Asmann Y, Klaus K, Nair K. An in vitro model for PCOS related insulin resistance: the effects of testosterone on phosphorylation of intracellular insulin signalling proteins in rat skeletal muscle primary culture. Fertil Steril 2005;84(Suppl 1):S30-31.
80. Corbould A. Chronic testosterone treatment induces selective insulin resistance in subcutaneous adipocytes of women J Endocrinol 2007;192:585-94.
81. Diamanti-Kandarakis E, Kandarakis H, Legro RS. The role of genes and environment in the etiology of PCOS. Endocrine 2006;30:19-26. Review.
82. Urbanek M, Woodroffe A, Ewens KG, Diamanti-Kandarakis E, Legro RS, Strauss JF 3rd et al. Candidate gene region for polycystic ovary syndrome on chromosome 19p13.2. J Clin Endocrinol Metab 2005;90:6623-9.
83. Diamanti-Kandarakis E, Piperi C. Genetics of polycystic ovary syndrome: searching for the way out of the labyrinth. Hum Reprod Update 2005;11:631-43. Review.
84. Morimoto S, Fernandez-Mejia C, Romero-Navarro G, Morales-Peza N, Díaz-Sánchez V. Testosterone effect on insulin content, messenger ribonucleic acid levels, promoter activity, and secretion in the rat. Endocrinology 2001;142:1442-7.
85. Morimoto S, Cerbón MA, Alvarez-Alvarez A, Romero-Navarro G, Díaz-Sánchez V. Insulin gene expression pattern in rat pancreas during the estrous cycle.Life Sci 2001;68:2979-85.