Hypothalamic releasing hormones: A novel role in pancreatic islet adaptation to pregnancy and gestational diabetes

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During normal pregnancy insulin resistance increases and maternal islets of Langerhans adapt by increasing both the insulin secretory response and the b-cell mass. Gestational diabetes (GDM) occurs when insulin secretary capacity is insufficient to meet the increased demands. The signals underlying this islet adaptation are currently not well understood, however placental-derived hormones and signalling through G protein-coupled receptors may be involved. This project will build on our recent studies identifying novel placental peptides with the potential to influence islet function during pregnancy. In particular, the project will focus on the potential role(s) for placental production of classical hypothalamic releasing hormones as mediators of maternal metabolic adaptation to pregnancy. Although this is a basic science project the results of these studies may have translational impact for the diagnosis and/or treatment of gestational diabetes.This project will use in vitro and in vivo methods to determine whether hypothalamic peptides produced by the placenta are involved in the adaptive responses of islet b-cells to the metabolic demands of pregnancy, by addressing sequential hypotheses.