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

Am J Physiol Endocrinol Metab. 2001 Aug;281(2):E392-9. doi: 10.1152/ajpendo.2001.281.2.E392.


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.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial

MeSH terms

  • Adult
  • Biopsy
  • Blood Glucose / metabolism
  • Body Mass Index
  • Chromatography, Thin Layer
  • Female
  • Glucose / pharmacokinetics
  • Glucose Clamp Technique
  • Humans
  • Insulin / blood
  • Insulin / pharmacology
  • Insulin Receptor Substrate Proteins
  • Insulin Resistance
  • Intracellular Signaling Peptides and Proteins
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Polycystic Ovary Syndrome / metabolism*
  • Polycystic Ovary Syndrome / pathology
  • RNA, Messenger / metabolism
  • Receptor, Insulin / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction*


  • Blood Glucose
  • IRS1 protein, human
  • IRS2 protein, human
  • Insulin
  • Insulin Receptor Substrate Proteins
  • Intracellular Signaling Peptides and Proteins
  • Phosphoproteins
  • RNA, Messenger
  • Phosphatidylinositol 3-Kinases
  • Receptor, Insulin
  • Glucose