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

Women with polycystic ovary syndrome (PCOS) are insulin resistant secondary to a postbinding defect in insulin signaling. Sequential euglycemic glucos e clamp studies at 40 and 400 mU.m(-2).min(-1) insulin doses with serial sk eletal muscle biopsies were performed in PCOS and age-, weight-, and ethnic ity-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 phosphatidylinos itol 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 sign ificant difference in the abundance of IR, IRS-1, or the p85 regulatory sub unit of PI 3K in PCOS (n = 14) compared with control (n = 12) muscle. The a bundance of IRS-2 was significantly increased (P < 0.05) in PCOS skeletal m uscle, suggesting a compensatory change. We conclude that there is a physio logically relevant defect in insulin receptor signaling in PCOS that is ind ependent of obesity and type 2 diabetes mellitus.