Insulin-stimulated release of d-chiro-inositol–containing inositolphosphoglycan mediator correlates with insulin sensitivity in women with polycystic ovary syndrome

Abstract

Some actions of insulin are mediated by inositolphosphoglycan mediators. Deficient release of a putative D-chiro-inositol-containing inositolphosphoglycan (DCI-IPG) mediator may contribute to insulin resistance in women with polycystic ovary syndrome (PCOS). Previously we demonstrated that oral DCI supplementation improved ovulation and metabolic parameters in women with PCOS. However, whether oral DCI mediates an increase in the release of the DCI-IPG mediator and an improvement in insulin sensitivity in women with PCOS is unknown. We conducted a randomized controlled trial of DCI supplementation vs. placebo in 11 women with PCOS who were assessed at two-time points, 6 weeks apart. Plasma DCI, DCI-IPG release during OGTT (AUCDCI-IPG) and insulin sensitivity (Si) by FSIVGTT were assessed at baseline and end-of-study. The study was terminated early due to a sudden unavailability of the study drug. However, in all subjects without regard to treatment assignment, there was a positive correlation between the change in AUCDCI-IPG / AUCInsulin ratio and the change in Si during the 6-week period (r=0.69, p=0.02), which remained significant after adjustment for BMI (p=0.022), and after further adjustment for BMI and treatment allocation (p=0.0261). This suggests that in women with PCOS, increased glucose-stimulated DCI-IPG release is significantly correlated with improved insulin sensitivity. The significant relationship between DCI-IPG release and insulin sensitivity suggests that the DCI-IPG mediator may be a target for therapeutic interventions in PCOS.

Evaluation of the In Vitro Inhibitory Activity of Rye-Buckwheat Ginger Cakes with Rutin on the Formation of Advanced Glycation End-Products (AGEs)

“…On the other hand, the data shown in our study confirm that rye-buckwheat ginger cakes enhanced with high rutin dosage obtained after dough fermentation may be recognized as DCI-rich product similarly to crackers made of tartary buckwheat flour as described by Yang & Ren [2008]. It should also be pointed out that a much higher dosage of DCI oral supplementation to observe the positive influence on decreasing insulin sensitivity was required to rich a fast-observed effect [Cheang et al, 2008].…”

“…Moreover, the important role of DCI glycans as a second messenger in insulin abnormal response was explained by Larner et al [2010]. Medical studies focused on oral DCI administration showed a positive correlation with a decreasing effect on insulin resistance in women with the polycystic ovary syndrome [Cheang et al, 2008;Takahama, et al 2011]. This finding highlighted the importance of food formulated with partial contribution of buckwheat flour that may be useful in diabetes and polycystic ovary syndrome intervention.…”

Inositol administration reduces oxidative stress in erythrocytes of patients with polycystic ovary syndrome

“…In the second pathway, either MYO or its epimerase-converted (39) chiro isoform DCI (44,45) constitutes IPGs (4), which are released from cell membrane glycosylphosphatidylinositols in response to insulin. Once released, IPGs can affect any tissues and cells implicated in insulin action (45), thus potentiating insulin effects (46). The significant reduction of Tyr-P levels in RBC found after MYO treatment and the reduction in insulin AUC confirm that this kind of therapy can improve IR, one of the typical features of PCOS (10).…”

Pioglitazone Therapy Increases Insulin-Stimulated Release of d-Chiro-Inositol-Containing Inositolphosphoglycan Mediator in Women with Polycystic Ovary Syndrome

“…6 Finally, we noted a significant positive association between change in Matsuda index and change in DCI-IPG released per unit of insulin, as has been demonstrated in our previous study with oral DCI. 8 A major strength of the study is its randomized, doubleblind placebo-controlled design, which provides internal validity to the findings of improved DCI-IPG release per unit of insulin after administering pioglitazone. In addition, these observations are novel since there is no such study in thiazolidinediones, although results are similar to those previously reported for metformin.…”

“…6,7 Insulin-stimulated release of DCI-IPG mediator correlates with insulin sensitivity in women with PCOS. 8 Furthermore, insulin action is coupled to release of DCI-IPG, an insulinomimetic second messenger that promotes glycogen synthesis. 9 Recently, it was reported that the coupling between insulin action and the release of the DCI-IPG mediator is selectively impaired in PCOS women with obesity this suggests that insulin-stimulated release of the DCI-IPG mediator is defective in obese women with PCOS.…”