Pioglitazone-d4 is intended for use as an internal standard for the quantification of pioglitazone by GC- or LC-MS. Pioglitazone is an agonist of the peroxisome proliferator-activated receptor γ (PPARγ; EC50 = ~500-600 nM for both human and murine PPARγ).1,2 It is selective for PPARγ over PPARα, exhibiting low level activation of PPARα at 1 ?M and 5.4-fold activation at a concentration of 10 ?M.1 Pioglitazone inhibits pyruvate oxidation and glucose production in hepatocytes when used at a concentration of 10 μM.3 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.4 It reduces the number of lesions in a transgenic rat adenocarcinoma of prostate (TRAP) model.5 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 GW 9662 .6
1.Sakamoto, J., Kimura, H., Moriyama, S., et al.Activation of human peroxisome proliferator-activated receptor (PPAR) subtypes by pioglitazoneBiochem. Biophys. Res. Commun.278(3)704-711(2000) 2.Willson, T.M., Brown, P.J., Sternbach, D.D., et al.The PPARs: From orphan receptors to drug discoveryJ. Med. Chem.43(4)527-550(2000) 3.Shannon, C.E., Daniele, G., Galindo, C., et al.Pioglitazone inhibits mitochondrial pyruvate metabolism and glucose production in hepatocytesFEBS J.284(3)451-465(2017) 4.Sugiyama, Y., Taketomi, S., Shimura, Y., et al.Effects of pioglitazone on glucose and lipid metabolism in Wistar fatty ratsArzneimittelforschung.40(3)263-267(1990) 5.Suzuki, S., Mori, Y., Nagano, A., et al.Pioglitazone, a peroxisome proliferator-activated receptor γ agonist, suppresses rat prostate carcinogenesisInt. J. Mol. Sci.17(12)pii: E2071(2016) 6.Zhao, Q., Wu, X., Yan, S., et al.The antidepressant-like effects of pioglitazone in a chronic mild stress mouse model are associated with PPARγ-mediated alteration of microglial activation phenotypesJ. Neuroinflammation13(1)259(2016)