Background
Pioglitazone belongs to the class of glitazones or thiazolidinediones, a series of oral anti-diabetic drugs. Pioglitazone is a ligand for peroxisome proliferator-activated receptor γ (PPARγ) that acts as a PPARγ agonist with EC50 of 0.93 and 0.99 μM for human and mouse PPARγ[1-2].
Pioglitazone (10 μM;4h) reversed the decrease in AMPK activity caused by high glucose in INS-1 cells [3]. Pioglitazone (50 μM;48h) also inhibited tumor cell proliferation in the multicellular tumor spheroid culture system (MCTS) system[4].
Pioglitazone (oral,10 or 30 mg/kg once daily for 14 days) improves insulin resistance and diabetes[5].Four weeks of pioglitazone (10 or 20 mg/kg, daily, from 20- to 24-week-old) treatment alleviated the high-fat diet (HFD)-induced glucose-metabolic dysfunctions, upregulation of ventral hippocampal glial fibrillary acidic protein (GFAP), reduction of the total process lengths and the number of branch points of the ventral hippocampal CA1 GFAP-immunoreactive astrocytes and depressive phenotypes in mice[6]. Pioglitazone (oral gavage;10 mg/kg; once daily for 4 weeks) significantly reduced body weight (BW) myocardial hypertrophy glucose levels and improved associated dyslipidemia[7].
参考文献:
[1]. Kuwabara K, Murakami K,et,al. A novel selective peroxisome proliferator-activated receptor alpha agonist, 2-methyl-c-5-[4-[5-methyl-2-(4-methylphenyl)-4-oxazolyl]butyl]-1,3-dioxane-r-2-carboxylic acid (NS-220), potently decreases plasma triglyceride and glucose levels and modifies lipoprotein profiles in KK-Ay mice. J Pharmacol Exp Ther. 2004 Jun;309(3):970-7. doi: 10.1124/jpet.103.064659. Epub 2004 Feb 24. PMID: 14982965.
[2]. Legchenko E, Chouvarine P, et,al. PPARγ agonist pioglitazone reverses pulmonary hypertension and prevents right heart failure via fatty acid oxidation. Sci Transl Med. 2018 Apr 25;10(438):eaao0303. doi: 10.1126/scitranslmed.aao0303. PMID: 29695452.
[3]. Karunakaran U, Elumalai S, et,al. Pioglitazone-induced AMPK-Glutaminase-1 prevents high glucose-induced pancreatic β-cell dysfunction by glutathione antioxidant system. Redox Biol. 2021 Sep;45:102029. doi: 10.1016/j.redox.2021.102029. Epub 2021 Jun 3. PMID: 34107382; PMCID: PMC8187239.
[4]. Gottfried E, Rogenhofer S, et,al. Pioglitazone modulates tumor cell metabolism and proliferation in multicellular tumor spheroids. Cancer Chemother Pharmacol. 2011 Jan;67(1):117-26. doi: 10.1007/s00280-010-1294-0. Epub 2010 Mar 9. PMID: 20217088.
[5]. Kubota N, Terauchi Y, et,al. Pioglitazone ameliorates insulin resistance and diabetes by both adiponectin-dependent and -independent pathways. J Biol Chem. 2006 Mar 31;281(13):8748-55. doi: 10.1074/jbc.M505649200. Epub 2006 Jan 23. PMID: 16431926.
[6]. Lam YY, Tsai SF, et,al. Pioglitazone rescues high-fat diet-induced depression-like phenotypes and hippocampal astrocytic deficits in mice. Biomed Pharmacother. 2021 Aug;140:111734. doi: 10.1016/j.biopha.2021.111734. Epub 2021 May 19. PMID: 34022606.
[7]. Elrashidy RA, Asker ME, et,al. Pioglitazone attenuates cardiac fibrosis and hypertrophy in a rat model of diabetic nephropathy. J Cardiovasc Pharmacol Ther. 2012 Sep;17(3):324-33. doi: 10.1177/1074248411431581. Epub 2012 Jan 18. PMID: 22261714.
Pioglitazone属于格列酮类或噻唑烷二酮类,是一系列口服降糖药。Pioglitazone是过氧化物酶体增殖体激活受体γ (PPARγ)的配体,作为PPARγ激动剂,对人和小鼠PPARγ的EC50分别为0.93和0.99 μM [1-2]。
Pioglitazone (10 μM;4h)可逆转INS-1细胞高糖引起的AMPK活性下降[3]。Pioglitazone (50 μM;48h)在多细胞肿瘤球体培养系统(MCTS)中也能抑制肿瘤细胞的增殖[4]。
Pioglitazone (oral,10 or 30 mg/kg once daily for 14 days)改善胰岛素抵抗和糖尿病[5]。Pioglitazone (10 or 20 mg/kg, daily, from 20-24-week-old) 治疗4周可减轻小鼠HFD诱导的葡萄糖代谢功能障碍、海马腹侧GFAP上调、海马腹侧CA1 GFAP免疫反应星形胶质细胞总过程长度和分支点数量减少以及抑郁表型[6]。Pioglitazone (oral gavage;10 mg/kg;once daily for 4 weeks) 显著降低体重(BW)、心肌肥厚、血糖水平和改善相关的血脂异常[7]。
Protocol
| Cell experiment [1]: |
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Cell lines
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INS-1 cells
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Preparation Method
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Cells were treated with pioglitazone (10 μM), with or without high glucose (30 mM).
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Reaction Conditions
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10 μM;4h
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Applications
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Pioglitazone reversed the decrease in AMPK activity caused by high glucose in INS-1 cells.
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| Animal experiment [2]: |
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Animal models
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ob/ob and adipo-/- ob/ob mice with a C57Bl/6 background
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Preparation Method
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10-30 mg/kg pioglitazone or vehicle (0.25% carboxymethylcellulose) was adnimistered to mice by oral gavage once daily for 14 consecutive days.
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Dosage form
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10-30 mg/kg; oral gavage; 14 days
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Applications
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10 mg/kg pioglitazone can significantly improve insulin resistance and diabetes in ob/ob mice, and administration of 30 mg/kg pioglitazone has better effects.
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参考文献:
[1]. Karunakaran U, Elumalai S, et,al. Pioglitazone-induced AMPK-Glutaminase-1 prevents high glucose-induced pancreatic β-cell dysfunction by glutathione antioxidant system. Redox Biol. 2021 Sep;45:102029. doi: 10.1016/j.redox.2021.102029. Epub 2021 Jun 3. PMID: 34107382; PMCID: PMC8187239.
[2]. Kubota N, Terauchi Y, et,al. Pioglitazone ameliorates insulin resistance and diabetes by both adiponectin-dependent and -independent pathways. J Biol Chem. 2006 Mar 31;281(13):8748-55. doi: 10.1074/jbc.M505649200. Epub 2006 Jan 23. PMID: 16431926.
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