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

Abstract

Background: Insulin resistance in women with polycystic ovary syndrome (PCOS) may be mediated, in part, by a deficiency in the insulin-stimulated release of a d-chiro-inositol-inositolphosphoglycan (DCI-IPG) mediator of insulin action. Supporting this idea, several studies have reported improved insulin sensitivity in both lean and obese women with PCOS after oral administration of DCI. Pioglitazone improves insulin sensitivity in women with PCOS, but it is unknown whether this may be contributed by enhanced insulin-stimulated release of the DCI-IPG second messenger. The study aimed to determine if pioglitazone increases release of biologically active DCI-IPG per unit insulin released during an oral glucose tolerance test (OGTT). Methods: A randomized, double-blind placebo-controlled trial was conducted in 32 women with PCOS at a tertiary referral center in Venezuela. The intervention comprised administration of pioglitazone 45 mg daily or matched placebo for 6 months. Outcome measures included area under curves (AUC) of DCI-IPG (AUC DCI-IPG ), insulin (AUC insulin ), and the ratio of AUC DCI-IPG to AUC insulin during a 2-hr OGTT. Results: After treatment with pioglitazone, AUC insulin during the OGTT decreased and whole body insulin sensitivity, as determined by the Matsuda index, increased significantly only in the pioglitazone group. The ratio of AUC DCI-IPG /AUC insulin increased in the pioglitazone group by 1.85-fold (P < 0.0001) with no significant change in the placebo group. Change in Matsuda index correlated with change in DCI-IPG released per unit of insulin during OGTT (r = 0.47, P < 0.01). Conclusion: In women with PCOS, pioglitazone increased insulin-stimulated release of the DCI-IPG second messenger of insulin action, which may contribute to its insulin-sensitizing effect in these women.

Reflections on inositol(s) for PCOS therapy: steps toward success

“…No such effect was noted, but they did observe that pioglitazione treatment significantly increased the ratio of DCI-IPG to insulin released during an OGTT (AUC DCI-IPG /AUC insulin ), which means that more DCI-IPG was released per unit insulin [34]. This result matches those previously observed with metformin [35].…”

Exploration and Development of PPAR Modulators in Health and Disease: An Update of Clinical Evidence

“…It is closely linked to chronic diseases like obesity, T2DM, and CVD. In PCOS patients, PPARγ agonists improve insulin sensitivity, hyperinsulinemia, glycemic control, and cardiovascular risk factors like lipid profiles and adiponectin level, but did not affect body weight and body mass index [309][310][311][312][313]. Importantly, pioglitazone also led to favorable changes in hirsutism, hyperandrogenism, and pregnancy occurrence [314,315].…”

Effect on Insulin-Stimulated Release of D-Chiro-Inositol-Containing Inositolphosphoglycan Mediator during Weight Loss in Obese Women with and without Polycystic Ovary Syndrome

“…In this current study, weight loss did not significantly improve AUC DCI-IPG /AUC insulin in either PCOS or normal women. In contrast, previous studies demonstrated that insulin sensitizers such as metformin [ 7 ] and rosiglitazone [ 11 ] improved the availability of DCI-IPG mediator release in women with PCOS.…”

“…Interventional studies with oral administration of DCI reported decreases in serum insulin and androgen levels, as well as improved ovulatory function in obese women with PCOS [ 8 – 10 ]. Conversely, administration of insulin sensitizers such as metformin [ 7 ] and pioglitazone [ 11 ] also increases insulin-stimulated release of DCI-IPG in women with PCOS.…”