The insulin signalling pathway in normal and gestationally diabetic pregnancies

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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.