Severe Impairment of Insulin Action in Adipocytes from Amenorrheic Subjects with Polycystic Ovary Syndrome

Adipose tissue was used to characterize the metabolic abnormality of insulin resistance in polycystic ovary syndrome (PCOS). Nine patients with PCOS were studied during a period of amenorrhea and confirmed to be chronically anovulatory by vaginal ultrasound and plasma progesterone measurements. These were compared with six age- and body mass index (BMI)-matched controls (BMI, 27.2 +/- 2.2 in PCOS and 24.7 +/- 2.3 in control subjects). Insulin receptor binding was measured and insulin action was assessed by measuring initial rates of 3-O-methylglucose uptake and by inhibition of lipolysis. The maximum specific insulin receptor binding was 0.62% +/- 0.12% and 1.78% +/- 0.18% per 10-cm2 cell surface (mean +/- SEM) in PCOS and control subjects, respectively (P < .001). Maximum rates of glucose transport were also impaired as compared with controls, with 3-O-methylglucose transport being 0.90 +/- 0.15 versus 1.57 +/- 0.28 pmol/10 cm2/5 s, respectively (P < .05). The concentration of insulin required for half-maximal stimulation of glucose uptake was 165 +/- 36 versus 32 +/- 10 pmol in PCOS and control subjects, respectively (P < .05). The maximum percentage lipolysis inhibition (mean +/- SEM) was 9.5% +/- 1.6% in PCOS and 28.3% +/- 7.2% in control patients, respectively (P < .01). These data demonstrate that there are both insulin binding and postreceptor defects in adipocytes from amenorrheic PCOS subjects. The degree of defect in adipocyte insulin action is greater than would have been anticipated from in vivo data.