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Chunk #7 — 2. Materials and Methods — 2.4. Isoglycemic-Hyperinsulinemic Clamp Studies

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The PPAR α / γ Agonist, Tesaglitazar, Improves Insulin Mediated Switching of Tissue Glucose and Free Fatty Acid Utilization In Vivo in the Obese Zucker Rat.
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Clamps were performed at different plateau levels of hyperinsulinemia from physiologically relevant to supraphysiological. Those denoted ClampL were performed at levels of hyperinsulinemia that were physiologically relevant for the particular group under study. In this case insulin infusion rates were tailored for each of the three groups of Zucker rats to produce plateau insulin levels corresponding to those observed in the freely fed postprandial state (2 h after onset of the dark phase) as determined in separate experiments: Lean 30, Obese 120, and Tesaglitazar 60 pmol/kglbm/min. To obtain information about insulin responsiveness ClampH clamps were performed at supraphysiological levels of hyperinsulinemia, with insulin infused at 10 times the corresponding ClampL rates for each group, that is, Lean 300, Obese 1200, and Tesaglitazar 600 pmol/kglbm/min. An additional ClampM was performed only in the Tesaglitazar group with an insulin infusion rate at 210 pmol/kglbm/min to achieve a plasma insulin level corresponding to the postprandial levels seen in the Obese group.