Hyperinsulinemia may mediate hyperleptinemia in gestational diabetic patients activating leptin expression in the trophoblast

ANTONIO PÉREZ PÉREZ; JULIETA L. MAYMÓ; PILAR GUADIX; CARMEN GONZÁLEZ; FERNANDO FABIANI; JOSÉ DUEÑAS; CECILIA L. VARONE; VÍCTOR SÁNCHEZ-MARGALET

Congreso; American Association for Clinical Chemistry AACC Annual Meeting. 2013; 2013

Hyperinsulinemia may mediate hyperleptinemia in gestational diabetic patients activating leptin expression in the trophoblast A. Pérez-Pérez1, J. Maymó2, P. Guadix1, C. González1, F. Fabiani1, J. L. Dueñas1, C. Varone2, V. SANCHEZ-MARGALET1. 1VIRGEN MACARENA UNIVERSITY HOSPITAL, SEVILLE, Spain, 2University of Buenos Aires, Buenos Aires, Argentina     Objectives: Gestational diabetes is the most frequent pathophysiological process associated with pregnancy. Leptin is a regulatory hormone in many cellular systems, including trophoblastic cells, where it is produced and may function as a trophic factor. Increased leptin levels are found in gestational diabetic women. In the present work we aimed to study circulating leptin and insulin levels in blood samples at 24-28 weeks of pregnancy and leptin expression in placenta from control pregnancies and gestational diabetic subjects. To assess a possible direct effect of insulin on leptin expression we carried out in vitro studies with trophoblast explants. Materials and Methods: We have studied serum levels insulin and leptin in blood samples obtained from 40 pregnant women with gestational diabetes, and 40 control pregnant women obtained at 24-28 weeks of pregnancy. Leptin and insulin levels were determined by ELISA method. Placenta from ten control pregnancies and ten gestational diabetic subjects were obtained after cessarean delivery. Leptin expression in placenta was assessed by qPCR and immnuoblot. Trophoblasts explants were obtained from control placenta and incubated with different concentrations of insulin. Quantifi cation of protein bands was determined by densitometry using Scion Image software (Scion Corporation, Washington, DC). The statistical signifi cance was assessed by one- way ANOVA followed by Bonferroni?s multiple comparison post hoc test and was calculated using the Graph Pad Instat computer program (San Diego, CA). A P-value < 0.05 was considered statistically signifi cant. Results: We have found that insulin and leptin levels are signifi cantly increased ingestational diabetic patient. Mean blodd insulin levels were 5.4±2.0 mU/ml in control group and 12.3±10 mU/ml in gestational diabetic group (p<0.05). Mean blood leptin levels were 25.0±14 ng/ml in control group and 54.0±31 ng/ml in gestational diabetic group. Leptin expression was also found signifi cantly (p<0.05) increased in placenta from gestational diabetics (about three fold), compared with control placenta. In vitro stimulation of trophoblasts explants with insulin showed a dose-dependent increase in both leptin gene expression and leptin protein amount. Conclusions: Both insulin and leptin levels are increased in serum from gestational diabetic patients. Moreover, leptin expression is increased in trophoblast from gestational diabetics, and insulin dose-dependently enhances leptin expression in cultured trophoblast explants. Therefore, hyperinsulinemia may mediate hyperleptinemia in gestational diabetes activating leptin expression in the trophoblast.