Proximal steps of glucose transport and phosphorylation are considered to contribute strongly to the pathogenesis of IR in obesity and type 2 DM (1-5). These scientific considerations might have potential therapeutic implications. The overall goal of this project is to provide clarity in separating the respective roles of these proximal steps of glucose metabolism. Glucose transport will be assessed using 11C-3-O-methyl glucose (half-life ~ 20 min; also referred to as 3-0-MG), an analog that is transported but not phosphorylated. 18F-2-deoxy-2-fluoro-glucose (half-life ~ 109 min; also referred to as FDG), will be used to assess glucose transport and glucose phosphorylation. The third tracer that will be used, 15O-H2O, will provide information on tissue perfusion. The challenge with the use of FDG to study insulin action in muscle has been to derive data on two biochemical steps from the tissue activity pattern of a single tracer; this has placed a higher reliance upon the modeling of the data. However, in this project, because of the use of three tracers and the differences in the metabolism of the two glucose analogs, we will be able to address with clear resolution the respective roles of transport and phosphorylation in the pathogenesis of IR in obesity and type 2 DM.