Pioglitazone

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 µM and 5.4-fold activation at a concentration of 10 µM.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 GW9662 (Item No. 70785).⁶

WARNING This product is not for human or veterinary use.

1. Sakamoto, J., Kimura, H., Moriyama, S., et al. Activation of human peroxisome proliferator-activated receptor (PPAR) subtypes by pioglitazone. Biochem. 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 discovery. J. 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 hepatocytes. FEBS 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 rats. Arzneimittelforschung. 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 carcinogenesis. Int. 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 phenotypes. J. Neuroinflammation 13(1), 259 (2016).

Shah, R., Farmer, L.A., Zilka, O., et al. Beyond DPPH: Use of fluorescence-enabled inhibited autoxidation to predict oxidative cell death rescue. Cell Chem. Biol. 26(11), 1594-1607 (2019).

Schmidleithner, L., Thabet, Y., Schönfeld, E., et al. Enzymatic activity of HPGD in Treg cells suppresses Tconv cells to maintain adipose tissue homeostasis and prevent metabolic dysfunction. Immunity 50(5), 1232-1248 (2019).