The insulin-sensitizing mechanism of myo-inositol is associated with AMPK activation and GLUT-4 expression in human endometrial cells exposed to a PCOS environment

Polycystic Ovary Syndrome (PCOS) is an endocrine-metabolic disorder characterized by hyperandrogenism and ovulatory dysfunction but also obesity and hyperinsulinemia. These characteristics induce an insulin-resistant state in tissues as endometrium, affecting its reproductive functions. Myo-inositol (MYO) is an insulin-sensitizer compound used in PCOS patients; however, its insulin-sensitizer mechanism is unclear. To understand the relationship of MYO with insulin action in endometrial cells, SMIT-1 (MYO-transporter) and MYO effect of protein-levels related to insulin pathway were evaluated. SMIT-1 was assessed in endometrial tissue from women with normal-weight, obesity, insulin-resistance and PCOS; additionally, using an in-vitro model of human endometrial cells exposed to environment resembling hyperinsulinic-obese-PCOS, MYO effect was evaluated on p-AMPK and GLUT-4 levels and glucose uptake by western blot, immunocytochemistry and confocal microscopy, respectively. SMIT-1 was detected in endometrial tissue from all groups and decreased in PCOS and obesity (p<0.05 vs normal-weight). In in-vitro model, PCOS conditions decreased p-AMPK levels being restored with MYO (p<0.05). The diminished GLUT-4 protein levels promoted by PCOS environment were restored by MYO through SMIT-1 and p-AMPK-dependent mechanism (p<0.05). Also, MYO restored glucose uptake in cells under PCOS condition through a p-AMPK dependent mechanism. Finally, these results were similar to those obtained with metformin treatment in the same in-vitro conditions. Consequently, MYO could be a potential insulin sensitizer by its positive effects in insulin-resistant tissues as PCOS-endometrium, acting through SMIT-1, provoking AMPK activation and elevated GLUT-4 levels and consequently, increasing glucose uptake by human endometrial cells. Therefore, MYO may be used as an effective option in insulin-resistant PCOS women.