Targeting GPCRs for the treatment of metabolic disease
The high prevalence of obesity and Type 2 diabetes worldwide has prompted substantial research on processes of energy utilisation and storage in several key metabolic organs/tissues including adipose tissue, cardiomyocytes and skeletal muscle. In Australia the incidence of Type 2 diabetes increased to 2.7 million in 2012. Diabetes is characterised by defects in the action of insulin in peripheral tissues and/or defects in pancreatic insulin secretion. Obesity has been implicated in additional diseases including inflammation, cardiovascular disease, cancer and arthritis. Increased physical activity and reduced intake of energy-rich foods often have limited long-term success, highlighting the need for pharmacological approaches to weight loss and glucose homeostasis. G protein-coupled receptors (GPCRs) represent attractive targets for the treatment of metabolic disease as they can elicit beneficial metabolic responses without interacting with the impaired insulin-stimulated signalling pathway.
Projects available include -
1. Mechanisms of GPCR-mediated glucose uptake in skeletal muscle and fat cells.
2. Role of mTOR complex 2 in glucose uptake and utilisation.
3. The role of inflammation in adipocyte function.
4. Recruitment and activation of inducible brown adipocytes.
We have state of the art facilities for primary cell culture, highthroughput cell-based assays, molecular biology including recombinant DNA and qPCR, confocal microscopy, measurement of cellular respiration and glycolysis, and in vivo studies using mouse and rat models of obesity and Type 2 diabetes.