Metabolic diseases, such as obesity and diabetes, increase the incidence of heart attacks and renal problems and accelerate the development of atherosclerosis. Investigations in this laboratory examine carbohydrate, lipid and protein metabolism in the whole body, in individual tissues (skeletal muscle, adipose tissue and liver) and in isolated cultured cells. One direction of these studies is focused on the causes of decreased sensitivity of cells to stimulation with insulin in various disease states. These studies involve measurement of insulin binding to its specific cellular receptors and the investigation of complex biochemical events which follow insulin binding and which mediate the action of insulin on various specific enzymes and membrane transporters in cells. The second direction of research is focused on regulation of protein metabolism in skeletal muscle with emphasis on mechanisms which could be used therapeutically to prevent excessive muscle protein degradation in catabolic disease states. The overall aim of this research is to increase the understanding of diabetes mellitus, obesity, trauma and other catabolic states at the subcellular and molecular levels and the development of scientifically sound treatment for these disease states.