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

在正常妊娠期间，胰岛素抵抗增加，母体胰岛通过增加胰岛素分泌反应和b细胞质量来适应。当胰岛素分泌能力不足以满足增加的需求时，就会发生妊娠糖尿病（GDM）。这种胰岛适应的信号目前还不清楚，但可能涉及胎盘源性激素和通过G蛋白偶联受体的信号传导。该项目将建立在我们最近的研究，确定新的胎盘肽与潜在的影响胰岛功能在怀孕期间。特别是，该项目将重点关注胎盘产生的经典下丘脑释放激素作为母体代谢适应妊娠的介质的潜在作用。虽然这是一个基础科学项目，但这些研究的结果可能对妊娠期糖尿病的诊断和/或治疗产生转化影响。本项目将使用体外和体内方法，通过解决序列假设，确定胎盘产生的下丘脑肽是否参与胰岛b细胞对妊娠代谢需求的适应性反应。

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.