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.

FIG. 1.

Plasma glucose levels at baseline, during fasting, and during low-dose and high-dose insulin steps for normal (NL) (♦) and polycystic ovary syndrome (PCOS) (▪) women. Of note, 2 normal and 2 PCOS women had too many unavailable glucose data and were excluded only for these analyses. Data are shown as means with standard error of the mean (SEM). ^aP ≤ 0.03 versus baseline within subgroup of PCOS or normal women (based on paired Student t-tests).

FIG. 2.

Plasma insulin levels at baseline (fasting, after 5 days of diazoxide) and during low-dose and high-dose insulin steps for normal (NL) (♦) and polycystic ovary syndrome (PCOS) (▪) women. Of note, 1 PCOS woman had too many unavailable insulin data and was excluded only for these analyses. Data are shown as means with standard error of the mean (SEM). *P < 0.04 versus normal women (based on unpaired Student t-tests). ^aP ≤ 0.04 versus baseline within a subgroup of PCOS or normal women (based on paired Student t-tests).

FIG. 3.

Plasma d-chiro-inositol-containing inositolphosphoglycan (DCI-IPG) bioactivity at baseline, during fasting, and during low-dose and high-dose insulin steps for normal (NL) (♦) and polycystic ovary syndrome (PCOS) (▪) women. Data are shown as means with SEM. *P ≤ 0.05 versus PCOS women (based on unpaired Student t-tests). ^aP < 0.05 versus baseline within subgroup of normal women (based on paired Student t-tests).

FIG. 4.

Area under the curves (AUCs) of plasma d-chiro-inositol-containing inositolphosphoglycan (DCI-IPG) bioactivity during each period of the low-dose and high-dose insulin steps for normal (NL) (□) and polycystic ovary syndrome (PCOS) (▪) women. AUCs were corrected for the duration of each period by dividing AUCs by the periods’ durations. Data are shown as means with standard error of the mean (SEM). *P ≤ 0.036 versus PCOS women (using the unpaired Student t-test).