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

Am J Physiol Endocrinol Metab. 2020 Feb 1;318(2):E237-E248. doi: 10.1152/ajpendo.00162.2019. Epub 2019 Dec 24.


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 such as the endometrium, affecting its reproductive functions. Myo-inositol (MYO) is an insulin-sensitizing compound used in PCOS patients; however, its insulin-sensitizing mechanism is unclear. To understand the relationship of MYO with insulin action in endometrial cells, sodium/myo-inositol transporter 1 (SMIT-1) (MYO-transporter), and MYO effects on protein levels related to the 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 an environment resembling hyperinsulinemic-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 the in vitro model, PCOS conditions decreased p-AMPK levels, while they were 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 through its positive effects on insulin-resistant tissues as PCOS-endometrium, acting through SMIT-1, provoking AMPK activation and elevated GLUT-4 levels and, consequently, increase glucose uptake by human endometrial cells. Therefore, MYO may be used as an effective treatment option in insulin-resistant PCOS women.

Keywords: AMPK; GLUT-4; endometrium; myo-inositol; polycystic ovary syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Adult
  • Cells, Cultured
  • Endometrium / cytology
  • Endometrium / metabolism*
  • Enzyme Activation
  • Female
  • Glucose / metabolism
  • Glucose Transporter Type 4 / biosynthesis*
  • Glucose Transporter Type 4 / genetics
  • Heat-Shock Proteins / metabolism
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Inositol / metabolism*
  • Insulin Resistance*
  • Metformin / pharmacology
  • Obesity / metabolism
  • Polycystic Ovary Syndrome / genetics
  • Polycystic Ovary Syndrome / metabolism*
  • Symporters / metabolism


  • Glucose Transporter Type 4
  • Heat-Shock Proteins
  • Hypoglycemic Agents
  • SLC2A4 protein, human
  • Symporters
  • SLC5A3 protein, human
  • Inositol
  • Metformin
  • AMP-Activated Protein Kinases
  • Glucose