Effects of metformin on rosiglitazone-induced cardiac hypertrophy in mice.
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.
Lee
Hsiu-Hao
HH
Department of Internal Medicine, Zhongxing Branch of Taipei City Hospital, Taipei, Taiwan.
Yeh
Ching-Hua
CH
Chen
Yu-Tai
YT
Chi
Tzong-Cherng
TC
Cheng
Juei-Tang
JT
Lo
Shih-Hsiang
SH
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
D045162:Thiazolidinediones; D000077154:Rosiglitazone; D008687:Metformin