Theme 10: Inflammation in Type 2 Diabetes and its Complications

Description:

The growing incidence of type 2 diabetes is a major medical concern. This metabolic syndrome is caused by the development of insulin resistance, which is normally a consequence of chronic obesity. During obesity, inflammation of adipose tissue (fat) and liver promote metabolic dysfunction and insulin resistance which results in type 2 diabetes. The onset of diabetes enhances the inflammatory response causing additional tissue damage to a number of organs including the heart, kidney, eye and nervous system. The overall aim of this theme is to create a greater understanding of the inflammatory process which takes place in tissues during the development of type 2 diabetes and its complications. Our research examines the role of a specific inflammatory cell (macrophages) in the development of obesity, insulin resistance and diabetic nephropathy. Our lab uses genetically modified mice and pharmacological inhibitors in models of obesity and type 2 diabetes to explore the molecular mechanisms by which macrophages promote injury. Our analyses include metabolic readouts, gene and protein expression in tissues, immunohistochemical assessment of pathology and cell culture assays of inflammation and metabolism.

1 The role of JNK signalling in macrophage-mediated tissue injury in type 2 diabetes.

Our animals studies have identified that obese mice which are genetically deficient in either JNK1 or JNK2 are protected from the development of insulin resistance and type 2 diabetes. This project will use previously collected tissues to examine how these deficiencies affect macrophage accumulation and their inflammatory responses in fat and the liver. Additional cell culture studies will utilise genetic deficiencies or pharmacological blockade to identify the importance of JNK signalling in specific interactions between macrophages and adipocytes or hepatocytes.