title: Effects of metformin on rosiglitazone-induced cardiac hypertrophy in mice.
abstract: Thiazolidinediones (TZD) can cause adipose tissue accumulation and myocardial hypertrophy. This study aimed to determine if combined Metformin (Glucophage) and Rosiglitazone (Avandia) could reduce the risk of heart failure caused by Rosiglitazone in BALB/c mice. BALB/c mice were treated with oral Rosiglitazone/Metformin twice daily for four weeks. Metformin or Rosiglitazone alone and non-treated mice acted as double control. Myocardial hypertrophy and associated side effects of the combined therapy were determined through isolated heart and body weights. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were applied to evaluate expression of sulfonylurea receptor 2A (SUR2A) and Kir 6.2. The activities of peroxisome proliferator activated receptor alpha (PPARalpha) in the myocardium were also observed. Rosiglitazone/Metformin decreased body weight gain and food intake, and inhibited an increasing adipose ratio but did not reduce myocardial hypertrophy. Rosiglitazone increased Kir6.2/SUR2A, Kir6.2/SUR2B, and PPARalpha gene expression. The Rosiglitazone/Metformin combination further increased these gene expressions, especially PPARalpha. Metformin inhibits obesity but has no effect in reducing myocardial hypertrophy caused by Rosiglitazone. Whether Metformin can reduce side effects of TZDs in humans warrants further study.
authors.affiliation: Department of Internal Medicine, Zhongxing Branch of Taipei City Hospital, Taipei, Taiwan.
authors.forename: Hsiu-Hao
authors.initials: HH
authors.lastname: Lee
authors.forename: Ching-Hua
authors.initials: CH
authors.lastname: Yeh
authors.forename: Yu-Tai
authors.initials: YT
authors.lastname: Chen
authors.forename: Tzong-Cherng
authors.initials: TC
authors.lastname: Chi
authors.forename: Juei-Tang
authors.initials: JT
authors.lastname: Cheng
authors.forename: Shih-Hsiang
authors.initials: SH
authors.lastname: Lo
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D006332:Cardiomegaly / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control; D004359:Drug Therapy, Combination; D004435:Eating / Q000187:drug effects / Q000502:physiology; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage* / Q000633:toxicity*; D015430:Weight Gain / Q000187:drug effects / Q000502:physiology
chemical_list: D045162:Thiazolidinediones; D000077154:Rosiglitazone; D008687:Metformin