Insulin and leptin signaling in placenta from gestational diabetic subjects

ANTONIO PÉREZ-PÉREZ; PILAR GUADIX; JULIETA L. MAYMÓ; JOSÉ DUEÑAS; CECILIA L. VARONE; MANUEL FERNÁNDEZ-SÁNCHEZ; VÍCTOR SÁNCHEZ-MARGALET

HORMONE AND METABOLIC RESEARCH

GEORG THIEME VERLAG KG

Lugar: Stuttgart; Año: 2015 vol. 48 p. 62 - 69

0018-5043

Insulin and leptin receptors are known to share signaling pathways, such as JAK2/STAT-3 (Janus kinase 2/signal transduction and activator of transcription 3), 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 three signaling pathways are activated in placenta from GDM patients to promote translation, involving the activation of leptin receptor. Now, we 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 normal pregnancies. Besides, we performed in vitro studies with insulin and leptin stimulation of trophoblast explants. 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 (0.1nM) potentiated the activation of signaling, whereas preincubation with maximal concentrations of insulin (10nM) and further stimulation with leptin showed negative effect. Similarly, 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 placenta from GDM, but insulin and leptin have negative effects upon overstimulation.