Peripubertal Hyperinsulinemia upregulates phosphatidylinositol 3-kinase/Akt pathway in rat ovaries

Objective: Polycystic ovary syndrome (PCOS) usually develops during peripuberty and is often associated with hyperinsulinemia. Paradoxically) hyperinsulinemic patients with PCOS develop peripheral insulin resistance but retain ovarian insulin sensitivity. We investigated the effect of peripubertal hyperinsulinemia on insulin signaling pathways in rat ovaries. Methods: Hyperinsulinemia was induced in peripubertal female rats by infusing insulin (0.14 IU/day) for 4 weeks. Control animals received normal saline. At autopsy, trunk blood was collected for insulin assay; ovaries were collectedfor examining the effect of hyperinsulinemia on phosphatidylinositol 3-kinase/Akt (PI3-K/Akt) and mitogen-activated protein kinase (MAPK/ERK1/2) pathways. Results: Compared with control, ovarian protein levels of total Akt, phospho-Akt, and phospho-glycogen synthase kinase-3 beta were upregulated and phospho-phosphatase and tensin homolog was downregulated in hyperinsulinemic animals. The MAPK/ERK1/2 pathway was unaffected. Conclusions: Peripubertal hyperinsulinemia upregulates the PI3-K/Akt pathway in rat ovaries. Ovarian insulin sensitivity in hyperinsulinemic patients with PCOS is potentially retained by this mechanism.