The insulin signalling pathway in normal and gestationally diabetic pregnancies

妊娠期糖尿病(GDM)是一种在怀孕期间发病或首次确诊的不同严重程度的糖耐量异常，影响5%至8%的孕妇，在澳大利亚每年有10,000多名妇女患病。这个项目的总体目标是增加我们对妊娠期糖尿病病因的了解。特别是，各种炎症途径在与妊娠期糖尿病相关的胰岛素抵抗所涉及的生化机制中的作用将被研究，这些途径代表了开发有效的临床管理策略的药物的新途径。尽管在理解胰岛素作用的分子机制和识别导致2型糖尿病胰岛素抵抗的缺陷方面取得了重大进展，但关于妊娠期糖尿病的现有数据仍然很少。更好地了解介导胰岛素作用的调控途径可能会导致确定治疗的分子靶点。此外，还将评估目前用于改善胰岛素信号转导的抗糖尿病疗法的临床效果。了解胰岛素信号是如何调节的，将对胰岛素抵抗和肥胖的治疗具有重大而重要的意义。由于多种促炎细胞因子在胰岛素信号转导中可能具有相似的作用，共享的细胞因子诱导的第二信使通路可能是治疗糖尿病的良好靶点。

Gestational Diabetes Mellitus (GDM), which is defined as glucose intolerance of variable severity with onset or first recognition during pregnancy, affects 5% to 8% of pregnancies, and represents more than 10,000 women annually in Australia. The overall aim of this project is to increase our understanding of the causes of gestational diabetes. In particular, the role of various inflammatory pathways in the biochemical mechanisms involved in insulin resistance associated with GDM will be examined, with these pathways representing novel approaches to developing agents for efficacious clinical management strategies for the management of GDM. Although major advances have been made in our understanding of the molecular mechanisms of insulin action and identification of the defects leading to insulin resistance in type 2 diabetes, there is still a paucity of data available concerning GDM. A better understanding of the regulatory pathways that mediate insulin action may lead to the identification of molecular targets for therapy. Furthermore, the clinical effectiveness of current anti-diabetic therapies to improve insulin signal transduction will be assessed. Understanding how insulin signalling is regulated will have major and important implications for the treatment of insulin resistance and obesity. As multiple pro-inflammatory cytokines may have similar effects on insulin signalling, the shared, cytokine-induced second messenger pathways may be excellent therapeutic targets for the treatment of diabetes.