Insulin and leptin cross-talk in placenta from healthy and gestational diabetic subjects

ANTONIO PÉREZ-PÉREZ; FLORA SÁNCHEZ-JIMÉNEZ; TERESA VILARIÑO GARCÍA; JENIFER MARTÍN-GONZÁLEZ; ANTONIO MANUEL CARMONA-FERNÁNDEZ; CECILIA L. VARONE; VÍCTOR SÁNCHEZ-MARGALET

Congreso; XXXVI Congreso de la Sociedad Española de Bioquímica y Biología Molecular; 2013

Insulin and leptin cross-talk in placenta from healthy and gestational diabetic subjects Antonio Pérez-Pérez1, Flora Sánchez-Jiménez1, Teresa Vilariño-García1, Jenifer Martín-González1, Antonio Manuel Carmona-Fernández1, Cecilia Varone2, Víctor Sánchez-Margalet11Hospital Universitario Virgen Macarena. Unidad de Gestión Clínica de Bioquímica clínica. Universidad de Sevilla, Sevilla, ES, 2Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires, Buenoa Aires, AR 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 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 gestational diabetic patients to promote translation, involving the activation of leptin receptor. Now, we raised the hypothesis that both leptin and insulin receptors might contribute to this activation in a positive cross-talk that may become negative when the system is overactivated.   To answer this question we studied the activation of leptin and insulin receptors in placenta from gestational diabetes and normal pregnancies. Besides, we performed in vitro studies with leptin stimulation of trophoblast explants.   We found that both leptin and insulin receptors are activated in placenta from gestational diabetes. In vitro stimulation with both leptin and insulin at submaximal doses (0.1 nM) potentiated the activation of signaling, whereas preincubation of trophoblasts with maximal concentrations of insulin (10 nM) and further stimulation with leptin showed negative cross-talk. Similarly, trophoblastic explants from gestational diabetic placenta, which presented high signaling levels, had a negative signaling cross-talk when incubated in vitro with leptin.     In conclusion, insulin and leptin receptors have positive cross-talk, contributing to high signaling levels in placenta from gestational diabetes, but insulin and leptin have negative cross-talk at maximal concentrations