Polycystic ovary syndrome is associated with tissue-specific differences in insulin resistance.
OBJECTIVE
The potential differential contributions of skeletal muscle and adipose tissue to whole body insulin resistance were evaluated in subjects with polycystic ovary syndrome (PCOS).


METHODS
Forty-two PCOS subjects and 15 body mass index-matched control subjects were studied. Insulin action was evaluated by the hyperinsulinemic/euglycemic clamp procedure. Isolated adipocytes and cultured muscle cells were analyzed for glucose transport activity; adipocytes, muscle tissue, and myotubes were analyzed for the expression and phosphorylation of insulin-signaling proteins.


RESULTS
Fifty-seven per cent of the PCOS subjects had impaired glucose tolerance and the lowest rate of maximal insulin-stimulated whole body glucose disposal compared to controls (P < 0.01). PCOS subjects with normal glucose tolerance had intermediate reduction in glucose disposal rate (P < 0.05 vs. both control and impaired glucose tolerance subjects). However, rates of maximal insulin-stimulated glucose transport (insulin responsiveness) into isolated adipocytes were comparable between all three groups, whereas PCOS subjects displayed impaired insulin sensitivity. In contrast, myotubes from PCOS subjects displayed reduced insulin responsiveness for glucose uptake and normal sensitivity. There were no differences between groups in the expression of glucose transporter 4 or insulin-signaling proteins or maximal insulin stimulation of phosphorylation of Akt in skeletal muscle, myotubes, or adipocytes.


CONCLUSIONS
Individuals with PCOS display impaired insulin responsiveness in skeletal muscle and myotubes, whereas isolated adipocytes display impaired insulin sensitivity but normal responsiveness. Skeletal muscle and adipose tissue contribute differently to insulin resistance in PCOS. Insulin resistance in PCOS cannot be accounted for by differences in the expression of selected signaling molecules or maximal phosphorylation of Akt.
Veterans Affairs San Diego Healthcare System, 3350 La Jolla Village Drive (111G), San Diego, California 92161, USA. tciaraldi@ucsd.edu
Theodore P
TP
Ciaraldi
Vanita
V
Aroda
Sunder
S
Mudaliar
R Jeffrey
RJ
Chang
Robert R
RR
Henry
D017667:Adipocytes / Q000378:metabolism; D000328:Adult; D005260:Female; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000032:analysis; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D018482:Muscle, Skeletal / Q000378:metabolism; D009928:Organ Specificity; D010766:Phosphorylation; D011085:Polycystic Ovary Syndrome / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
D051275:Glucose Transporter Type 4; D007328:Insulin; C495692:SLC2A4 protein, human; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose