MAPK1 and Hyperinsulinemia: The ERK2-PI3K/AKT and MAPK/ERK pathways in classic insulin-sensitive tissues target ovarian tissue, and disruption of the signaling pathway can lead to decreased insulin sensitivity and compensative hyperinsulinemia in PCOS rats.[54,55] GABA and positive-feedback GABA receptor regulatory steroids, such as isoprogesterone, stimulate food intake and weight gain.