Diuretics prevent thiazolidinedione-induced cardiac hypertrophy without compromising insulin-sensitizing effects in mice

Cherng Shyang Chang, Pei Jane Tsai, Junne Ming Sung, Ju Yi Chen, Li Chun Ho, Kumar Pandya, Nobuyo Maeda, Yau Sheng Tsai

研究成果: Article

10 引文 斯高帕斯(Scopus)

摘要

Much concern has arisen regarding critical adverse effects of thiazolidinediones (TZDs), including rosiglitazone and pioglitazone, on cardiac tissue. Although TZD-induced cardiac hypertrophy (CH) has been attributed to an increase in plasma volume or a change in cardiac nutrient preference, causative roles have not been established. To test the hypothesis that volume expansion directly mediates rosiglitazone-induced CH, mice were fed a high-fat diet with rosiglitazone, and cardiac and metabolic consequences were examined. Rosiglitazone treatment induced volume expansion and CH in wild-type and PPARγ heterozygous knockout (Pparg+/-) mice, but not in mice defective for ligand binding (PpargP465L/+). Cotreatment with the diuretic furosemide in wild-type mice attenuated rosiglitazone-induced CH, hypertrophic gene reprogramming, cardiomyocyte apoptosis, hypertrophy-related signal activation, and left ventricular dysfunction. Similar changes were observed in mice treated with pioglitazone. The diuretics spironolactone and trichlormethiazide, but not amiloride, attenuated rosiglitazone effects on volume expansion and CH. Interestingly, expression of glucose and lipid metabolism genes in the heart was altered by rosiglitazone, but these changes were not attenuated by furosemide cotreatment. Importantly, rosiglitazone- mediated whole-body metabolic improvements were not affected by furosemide cotreatment. We conclude that releasing plasma volume reduces adverse effects of TZD-induced volume expansion and cardiac events without compromising TZD actions in metabolic switch in the heart and whole-body insulin sensitivity.

原文English
頁(從 - 到)442-453
頁數12
期刊American Journal of Pathology
184
發行號2
DOIs
出版狀態Published - 2014 二月 1

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

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