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Pioglitazone is an agonist of the peroxisome proliferator-activated receptor γ (PPARγ; EC50 = ~500-600 nM for both human and murine PPARγ). It is selective for PPARγ over PPARα, exhibiting low level activation of PPARα at 1 μM and 5.4-fold activation at a concentration of 10 μM. Pioglitazone inhibits pyruvate oxidation and glucose production in hepatocytes when used at a concentration of 10 μM. In vivo, pioglitazone (0.3-3 mg/kg per day) reduces hyperglycemia, hyperlipidemia, and hyperinsulinemia in a dose-dependent manner in male Wistar fatty rats. It reduces the number of lesions in a transgenic rat adenocarcinoma of prostate (TRAP) model. Pioglitazone (2.5 mg/kg) also decreases production of neuroinflammatory cytokines and reduces immobility in the forced swim and tail suspension tests in a mouse model of chronic mild stress, indicating antidepressant-like activity that can be reversed by the PPARγ antagonist GW9662 .

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