The insulin signalling pathway in normal and gestationally diabetic pregnancies

妊娠期糖尿病（GDM）定义为在妊娠期间发病或首次发现的不同严重程度的葡萄糖耐受不良，影响5%至8%的妊娠，在澳大利亚每年有超过10，000名妇女。该项目的总体目标是增加我们对妊娠糖尿病原因的了解。特别是，各种炎症途径在与GDM相关的胰岛素抵抗的生化机制中的作用将被检查，这些途径代表了开发GDM有效临床管理策略的药物的新方法。虽然我们已经取得了重大进展，在我们的胰岛素作用的分子机制的理解和识别的缺陷，导致胰岛素抵抗的2型糖尿病，仍然是一个缺乏数据有关GDM。更好地了解调节胰岛素作用的调节途径可能会导致治疗的分子靶点的确定。此外，还将评估当前抗糖尿病治疗改善胰岛素信号转导的临床有效性。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产生重大而重要的影响。由于多种促炎性细胞因子对胰岛素信号传导具有相似的作用，因此共享的、精氨酸诱导的第二信使途径可能是治疗糖尿病的极好的治疗靶点。

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.