obese rat which was generally not possible in untreated animals due to a virtual absence of insulin effect. For the Tesaglitazar treated group the EC50 for white fat, diaphragm and RG were 0.7 nM (95% CI 0.4–1.0), 1.7 nM (1.1–2.7), and 3.5 nM (0.6–21.4), respectively. (For comparison the EC50 values in Lean animals were for white fat, diaphragm, and RG 0.5 nM (95% CI 0.4–0.7), 0.9 nM (0.7–1.2), and 1.4 nM (0.9–2.1), resp.). By contrast in Obese only in white fat could an estimate of EC50 be made: 9.6 nM (6.4–14.6). The improvement in insulin action with tesaglitazar treatment was also manifested in a general restoration of insulin responsiveness with R g′ at supraphysiologic insulin levels substantially higher in skeletal muscle and white fat (Figure 3 and Table 4) in Tesaglitazar compared to Obese. In the Tesaglitazar group, maximal insulin effects on both whole body glucose metabolism and R g′ in insulin responsive tissues were actually generally achieved under ClampM conditions, performed at insulin levels equivalent to those seen postprandially in untreated obese Zuckers (Tables 3 and 4).
