Uncoupling Between Insulin and Release of a d - Chiro -Inositol–Containing Inositolphosphoglycan Mediator of Insulin Action in Obese Women With Polycystic Ovary Syndrome

Abstract

Background:

Obese women with polycystic ovary syndrome (PCOS) manifest impaired insulin-stimulated release of a d-chiro-inositol-containing inositolphosphoglycan (DCI-IPG) insulin mediator during oral glucose tolerance testing (OGTT), which appears to be restored by the administration of metformin. This suggests that either obesity or PCOS is associated with a defect in the coupling of the stimulation of the insulin receptor by insulin to the release of the DCI-IPG mediator. The objective of this study was to compare the release of bioactive DCI-IPG between normal nonobese women and obese PCOS women during stimulation with two different concentrations of insulin when glucose levels are clamped.

Methods:

We performed a cross-sectional case–control study at the clinical research center of an academic medical center. A two-step euglycemic–hyperinsulinemic clamp was carried out in 8 nonobese normal and 8 obese PCOS women, during which DCI-IPG bioactivity was monitored.

Results:

At baseline, PCOS women were significantly more obese, hyperinsulinemic, and insulin resistant than the controls. During the clamp studies, DCI-IPG bioactivity increased significantly over the first 45 min of the low-insulin step of the clamp in normal nonobese women (P = 0.046) and then decreased to baseline levels; DCI-IPG increased again after initiation of the high-insulin step (P = 0.029). Despite higher insulin levels during the clamp in PCOS women, DCI-IPG bioactivity remained flat throughout both insulin steps and was thus significantly lower than in controls during the initial periods of both steps.

Conclusions:

The coupling between insulin action and the release of the DCI-IPG mediator is selectively impaired in obese PCOS women, which may contribute to the insulin resistance in these women.