INSULIN RESISTANCE IN POLYCYSTIC-OVARY-SYNDROME - DECREASED EXPRESSION OF GLUT-4 GLUCOSE TRANSPORTERS IN ADIPOCYTES

We have found that women with polycystic ovary syndrome (PCOS) have decreased sensitivity and responsiveness to insulin. The present study was performed to determine whether this impaired insulin responsiveness was associated with diminished GLUT-4 glucose transporter content in adipocytes. Insulin-stimulated glucose transport and GLUT-4 abundance were measured in abdominal adipocytes from obese (n = 9) and lean (n = 7) PCOS as well as obese (n = 8) and lean (n = 8) control women matched for age and weight. No woman had impaired glucose tolerance. The maximal insulin-stimulated increment in adipocyte glucose transport was independently decreased by obesity and by PCOS. As expected, GLUT-4 content in adipocyte membranes was decreased in obesity (by 40%, P less-than-or-equal-to 0.01). GLUT-4 content was also significantly decreased in PCOS (by 36%, P less-than-or-equal-to 0.01), independent of obesity. There was a highly significant correlation (R = 0.66, P less-than-or-equal-to 0.001) between GLUT-4 content and insulin-stimulated glucose transport in adipocytes from individual women across the study population. We conclude that the diminished adipocyte insulin responsiveness in PCOS is associated with decreased GLUT-4 abundance. This represents a newly recognized phenotypic feature of the insulin resistance of PCOS. Moreover, in human adipocytes, GLUT-4 abundance is highly correlated with insulin responsiveness.