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1 Division of Women's Health, Departments of Medicine and of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, Massachusetts 02115; and 2 Section of Diabetes and Metabolism, Department of Medicine, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033
Women with polycystic ovary syndrome (PCOS) are
insulin resistant secondary to a postbinding defect in insulin
signaling. Sequential euglycemic glucose clamp studies at 40 and 400 mU · m
2 · min1 insulin
doses with serial skeletal muscle biopsies were performed in PCOS and
age-, weight-, and ethnicity-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 phosphatidylinositol 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
significant difference in the abundance of IR, IRS-1, or the p85
regulatory subunit of PI 3K in PCOS (n = 14) compared with control (n = 12) muscle. The abundance of IRS-2
was significantly increased (P < 0.05) in PCOS
skeletal muscle, suggesting a compensatory change. We conclude that
there is a physiologically relevant defect in insulin receptor
signaling in PCOS that is independent of obesity and type 2 diabetes mellitus.
insulin resistance; signal transduction; phosphatidylinositol 3-kinase; insulin receptor substrate-1; insulin receptor substrate-2
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