” Basic Science and the Placenta Symposium Session. Presentación titulada: The Feto-Placental Insulin-IGF System in Diabetes

DESOYE G, HIDEN U, JAWERBAUM A, WHITE V

Estambul, Turquía

Simposio; 4th International Symposium on Diabetes and Pregnancy; 2007

International Association of Diabetes and Pregnancy

The placenta separates maternal from fetal blood and, hence, is exposed to regulatory molecules such as growth factors and cytokines in both blood streams. Insulin (I) and insulin-like-growth factors (IGF) -I and -II have received particular attention, because of their well-established mitogenic potency and their elevated levels in conditions associated with fetal/placental overgrowth such as in (pre)gestational diabetes. Moreover, their receptors (R) are expressed in the placenta.IR location varies with gestational age. Early in gestation IR are predominantly expressed on the syncytiotrophoblast facing the maternal circulation. At the end of gestation the majority of receptors is located on the placental endothelium and, hence, is in contact with the fetal circulation. This developmental change in receptor location is paralleled by a change in isoform expression favouring the IGF-II signalling IR on the fetal side, thus enabling fetal IGF-II to regulate yet unknown anabolic functions in the placenta.Maternal insulin can stimulate placental growth via activation of the MAPK pathway, whereas fetal insulin will activate metabolic pathways such as accumulation of glycogen, a well known feature of the placenta in diabetes. Diabetes is accompanied by a change in IR splicing favouring the long IR isoform that mediates mitogenic effects. This will further enhance the growth promoting role of insulin on the placenta.IGF-IR are predominantly located on the basal membrane of the syncytiotrophoblast thus allowing access of fetal IGF-I to the receptor. This strongly argues also for a fetal-placental IGF-I axis that may be modified in diabetes.