According to the World Health Organization, the type two diabetes epidemic will continue well into the 21st century and affect people in all age groups. A major metabolic consequence of obesity is insulin resistance, which can lead to  uncontrolled glucose production in the liver. This significantly contributes to the onset of type 2 diabetes. The etiology of insulin resistance is still poorly understood.
It is therefore the aim of ‘LiverX’ to systematically collect and analyse quantitative and dynamic data of the important metabolic networks at the levels of single cells, organs and whole organisms. Together with clinical data of patients this knowledge will be used to develop mathematical models of insulin resistance. Alterations in metabolic control are not unique to type two diabetes but underlie many other metabolism-related disorders including cancer. The data generated in this project should therefore have applications far beyond the project and provide novel perspectives for diagnostics and therapeutics.

This project is a central component of ongoing programs in medical systems biology at the Competence Center for Systems Physiology & Metabolic Diseases, dedicated to molecular systems approaches to the regulation of metabolism and disease states related to the metabolic syndrome or SyndromeX. Existing programs of this center are focussing on the insulin-secreting pancreatic ß-cell and the energy storing adipocyte. As the liver is the principal organ integrating glucose and fat metabolism in response to circulating insulin and glucagons, the current proposal ideally integrates in the strategic scientific goals of CC-SPMD. Because of its anatomical and physiological characteristics, the liver also provides a unique opportunity to mathematically model its complex signaling and metabolic responses to environmental changes in the context of single cells and at the organismal level and to relate emerging paradigms to whole body physiology and disease.

• Publications by SystemsX.ch (overview)