PDF(Pubmed)
Abstract：
Pioglitazone is class of thiazolidinediones that activates peroxisome proliferator-activated receptors (PPARs) in adipocytes to improve glucose metabolism and insulin sensitivity and has been used as a treatment for type 2 diabetes. However, the underlying mechanisms of associated pioglitazone-induced effects remain unclear. Our study aimed to investigate endogenous metabolite alterations associated with pioglitazone administration in healthy male subjects using an untargeted metabolomics approach. All subjects received 30 mg of pioglitazone once daily in the assigned sequence and period. Urine samples were collected before pioglitazone administration and for 24 h after 7 days of administration. A total of 1465 compounds were detected and filtered using a coefficient of variance below 30% and 108 metabolites were significantly altered upon pioglitazone administration via multivariate statistical analysis. Fourteen significant metabolites were identified using authentic standards and public libraries. Additionally, pathway analysis revealed that metabolites from purine and beta-alanine metabolisms were significantly altered after pioglitazone administration. Further analysis of quantification of metabolites from purine metabolism, revealed that the xanthine/hypoxanthine and uric acid/xanthine ratios were significantly decreased at post-dose. Pioglitazone-dependent endogenous metabolites and metabolic ratio indicated the potential effect of pioglitazone on the activation of PPAR and fatty acid synthesis. Additional studies involving patients are required to validate these findings.
摘要：
吡格列酮是一类噻唑烷二酮，可激活脂肪细胞中的过氧化物酶体增殖物激活受体（PPAR）以改善葡萄糖代谢和胰岛素敏感性，已被用作2型糖尿病的治疗方法。然而,吡格列酮诱导作用的相关机制尚不清楚.我们的研究旨在使用非靶向代谢组学方法研究健康男性受试者中与吡格列酮给药相关的内源性代谢物改变。所有受试者以指定的顺序和时期每天一次接受30mg吡格列酮。在施用吡格列酮之前和施用7天后24小时收集尿样。使用低于30%的变异系数检测并过滤了总共1465种化合物,并且通过多变量统计分析,吡格列酮施用后108种代谢物显著改变。使用真实的标准和公共图书馆鉴定了14种重要的代谢物。此外,途径分析显示,吡格列酮给药后,嘌呤和β-丙氨酸代谢的代谢产物发生显著改变.嘌呤代谢产物的进一步定量分析，显示黄嘌呤/次黄嘌呤和尿酸/黄嘌呤比率在给药后明显降低。吡格列酮依赖的内源性代谢产物和代谢比例表明吡格列酮对PPAR激活和脂肪酸合成的潜在影响。需要涉及患者的其他研究来验证这些发现。
