Defects in insulin receptor signaling in vivo in the polycystic ovary syndrome (PCOS).
Level 4 - case-series / case-control
Matched case-control physiological study
PubMed 11440917 · doi:10.1152/ajpendo.2001.281.2.E392
What was done
Sequential euglycemic glucose clamp studies at 40 and 400 mU·m⁻²·min⁻¹ insulin doses with serial skeletal muscle biopsies were performed in women with polycystic ovary syndrome (PCOS) and age-, weight-, and ethnicity-matched control women. Steady-state insulin levels, insulin-mediated glucose disposal, and the abundance and activity of key insulin signaling proteins (IR, IRS-1, IRS-2, and PI 3-kinase) in skeletal muscle were evaluated.
What was found
Steady-state insulin levels did not differ between groups, but insulin-mediated glucose disposal was significantly decreased in PCOS women (P < 0.05). IRS-1-associated PI 3-kinase activity was significantly decreased in PCOS skeletal muscle (n = 12) compared with control muscle (n = 8; P < 0.05). There were no significant differences in the protein abundance of IR, IRS-1, or the p85 regulatory subunit of PI 3-kinase between PCOS (n = 14) and control (n = 12) muscle, but IRS-2 abundance was significantly increased in PCOS (P < 0.05). Absolute values and effect sizes were not provided in the abstract.
Why it matters
This study provides direct in vivo evidence that insulin resistance in PCOS involves a post-receptor defect in skeletal muscle IRS-1/PI 3-kinase signaling that is independent of obesity and type 2 diabetes.
Limits
The sample size was very small (up to 14 PCOS and 12 controls), and numerical values, standard deviations, and exact effect sizes were omitted from the abstract. The observational case-control design demonstrates biochemical correlation rather than causal progression.
Cited by
- supports Women with PCOS typically exhibit impaired glucose disposal and insulin resistance similar to individuals with type 2 diabetes.