My main research interests are in the areas of insulin and exercise signalling, insulin resistance and glucose metabolism in physiological and pathophysiological conditions. My research brings new cellular and molecular approaches to study the pathophysiology of chronic metabolic conditions and helps understand the impact of nutritional and physiological changes on the development and treatments of insulin resistance, type 2 diabetes and metabolic syndrome.

For several years now, I have investigated the mechanism of glucose transporter (GLUT4) vesicle trafficking. Insulin signalling plays a pivotal role in this process. Therefore, mapping GLUT4 trafficking is critical to understanding the cellular defects in diabetes. The identification of the key molecules linking insulin signalling and GLUT4 trafficking is a major challenge in the GLUT4 research field. The reason this challenge remains is mainly due to the complexity of the insulin-signalling cascade. The next major challenge in this area is to identify the small GTPases of the Rab family of proteins responsible for insulin induced GLUT4 translocation. This is the aim of my current research grant from the MRC.

To achieve this aim I am using a cross-disciplinary approach, combining cellular and molecular studies with a human intervention study in order to translate the molecular findings into whole body physiological functions. We are using cellular models of adipose cells to investigate the molecular interactions between Rab3 and other proteins in the cell that act as links between insulin action at its receptor and the GLUT4 transporter. We will investigate how these interactions are affected by treatment with proinflammatory cytokines, including TNFα, or other molecules known to induce the state of insulin resistance. These experiments will allow us to understand the mechanisms of action of Rab3 in the context of the development of the insulin-resistant state. We will also investigate in humans, undergoing a diet and exercise intervention programme, whether Rab3 is affected in a manner that reveals underlying mechanisms involved in the control of insulin sensitivity in adipose tissues and skeletal muscles. The outcome from this project will have important implications for our understanding of the mechanisms of the development of peripheral tissues insulin resistance and for the development of new, targeted therapies for treatment of insulin resistant subjects and people with type 2 diabetes. This study will also be a springboard to inform further investigations into the development of insulin resistance and the cross-talk between chronic inflammation, obesity and the onset of type 2 diabetes.

Identification of new biomarkers of insulin resistance and type 2 diabetes.
Development of human skeletal muscle satellite cell model for in vitro assessment of metabolic health.