It has been shown that tesaglitazar ameliorates insulin resistance in animal models [16, 17], as well as centrally obese/hypertriglyceridemic nondiabetic humans [28, 29] and patients with type 2 diabetes [30]; however, the tissue loci of these effects have not been reported. The present study demonstrates that the tesaglitazar induced whole body insulin sensitization was due to a widespread restoration of insulin action. Thus tesaglitazar greatly increased insulin's ability to suppress HGO (Figure 1) and also restored insulin's ability to stimulate skeletal muscle glucose uptake (Table 4). This latter action was of a profound nature with untreated obese Zuckers lacking any robust dose response relationship between skeletal muscle glucose uptake and insulin level. Treatment succeeded in restoring a clear dose response relationship including a remarkable increase in the maximal insulin responsiveness in skeletal muscle (Figure 3). Not only did tesaglitazar enhance insulin stimulated skeletal muscle glucose uptake but also normalized the rate of insulin stimulated glycogen synthesis in this tissue to that seen in the lean Zuckers (Table 7), albeit at a higher insulin level. The effects of tesaglitazar on augmenting
