Hyperinsulinemia Stimulates Angiogenesis of Human Fetoplacental Endothelial Cells: A Possible Role of Insulin in Placental Hypervascularization in Diabetes Mellitus

Context: The insulin/IGF system regulates fetal and placental growth and development. In a pregnancy complicated by maternal diabetes, placentas are hypervascularized and fetal insulin levels are elevated. In the fetal circulation, insulin can act on the placenta through insulin receptors present on the fetoplacental endothelial cells. Objective: We hypothesized that insulin exerts proangiogenic effects on the fetoplacental endothelial cells, thereby contributing to the placental hypervascularization in diabetes. Design: The effect of insulin on angiogenesis and proliferation of human fetoplacental endothelial cells was investigated by a 2-dimensional network formation assay, staining for actin fibers, automatic cell counting, and cell cycle analysis. The signaling pathways involved were identified using antibodies against activated signaling proteins and pharmacological inhibitors. Results: Insulin enhanced network formation by 23% (P < .05%) and caused actin reorganization. Insulin stimulated (P < .05) ...