Defects in insulin receptor signaling in vivo in the polycystic ovary syndrome (PCOS)

Andrea Dunaif*, Xinqi Wu, Anna Lee, Evanthia Diamanti-Kandarakis

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

279 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)E392-E399
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number2 44-2
StatePublished - 2001


  • Insulin receptor substrate-1
  • Insulin receptor substrate-2
  • Insulin resistance
  • Phosphatidylinositol 3-kinase
  • Signal transduction

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)


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