Molecular defects of insulin action in the polycystic ovary syndrome: possible tissue specificity

Abstract

Insulin resistance is a highly common occurrence in PCOS. To determine the cellular and molecular mechanisms of this insulin resistance we studied subcutaneous abdominal adipocytes isolated from age and weight matched normal cycling (NC) and PCOS subjects. Insulin resistance in PCOS adipocytes was manifested as a reduction in insulin sensitivities for stimulation of glucose transport and suppression of catecholamine-activated lipolysis with no impact on final hormone responsiveness. Insulin sensitivity in adipocytes could be normalized by the addition of an adenosine analog. A number of key steps in insulin signaling pathways receptor autophosphorylation, IRS-1 phosphorylation, PI3-kinase activation and Akt phosphorylation--were found to display normal sensitivity and responsiveness in PCOS adipocytes. Insulin action measured in cultured fibroblasts was similar in NC and PCOS cells. Insulin resistance in PCOS involves tissue and response-specific defects in insulin signal transduction that remain to be identified. Interventions that can increase insulin sensitivity, such as adenosine, may have therapeutic potential in treating the unique insulin resistance of PCOS.