RT Journal Article T1 Insulin and Leptin Signaling in Placenta from Gestational Diabetic Subjects. A1 Pérez-Pérez, A. A1 Guadix, P. A1 Maymó, J. A1 Dueñas, J. L. A1 Varone, C. A1 Fernández-Sánchez, M. A1 Sánchez-Margalet, V. K1 Leptin K1 Insulin K1 Signal transduction K1 Gestational diabetes K1 Placenta K1 Proteínas quinasas activadas por mitógenos K1 Fosfatidilinositol 3-Quinasas K1 Trofoblastos AB Insulin and leptin receptors are known to share signaling pathways, such as JAK2/STAT-3 (Janus kinase2/signal transduction and activator of transcription3), MAPK (Mitogen activated protein kinase), and PI3K (phosphoinositide 3-kinase). Both positive and negative cross-talk have been previously found in different cellular systems. Gestational diabetes (GDM) is a pathophysiological state with high circulating levels of both insulin and leptin. We have previously found that these 3 signaling pathways are activated in placenta from GDM patients to promote translation, involving the activation of leptin receptor. Now, we have tested the hypothesis that both leptin and insulin receptors might contribute to this activation in a positive way that may become negative when the system is overactivated. We studied the activation of leptin and insulin receptors in placenta from GDM and healthy pregnancies. We have also performed in vitro studies with insulin and leptin stimulation of trophoblast explants from healthy placenta. We have found that both leptin and insulin receptors are activated in placenta from GDM. In vitro stimulation of trophoblast explants with both leptin and insulin at submaximal doses (0.1 nM) potentiated the activation of signaling, whereas preincubation with maximal concentrations of insulin (10 nM) and further stimulation with leptin showed negative effect. Trophoblastic explants from GDM placenta, which presented high signaling levels, had a negative signaling effect when further incubated in vitro with leptin. In conclusion, insulin and leptin receptors have positive effects on signaling, contributing to high signaling levels in GDM placenta, but insulin and leptin have negative effects upon overstimulation. PB Thieme Publishing SN 0018-5043 YR 2016 FD 2016-01 LK http://hdl.handle.net/10668/2210 UL http://hdl.handle.net/10668/2210 LA en NO Pérez-Pérez A, Guadix P, Maymó J, Dueñas JL, Varone C, Fernández-Sánchez M, et al. Insulin and Leptin Signaling in Placenta from Gestational Diabetic Subjects. Horm. Metab. Res. 2016; 48(1):62-9 NO Journal Article; DS RISalud RD Dec 25, 2024