Metformin Inhibits Isoproterenol-induced Cardiac Hypertrophy in Mice
Metformin Inhibits Isoproterenol-induced Cardiac Hypertrophy in Mice
- Hye-Na Cha Jung Hyun Choi Yong-Woon Kim Jong-Yeon Kim Myun-Whan Ahn So-Young Park
- 대한생리학회-대한약리학회
- The Korean Journal of Physiology & Pharmacology
- 제14권 제6호
- 등재여부 : KCI등재
- 2010.01
- 377 - 384 (8 pages)
The present study examined whether metformin treatment prevents isoporterenol-induced cardiac hypertrophy in mice. Chronic subcutaneous infusion of isoproterenol (15 mg/kg/24 h) for 1 week using an osmotic minipump induced cardiac hypertrophy measured by the heart-to-body weight ratio and left ventricular posterior wall thickness. Cardiac hypertrophy was accompanied with increased interleukin-6 (IL-6), transforming growth factor (TGF)-Ղ, atrial natriuretic peptide (ANP), collagen I and III, and matrix metallopeptidase 2 (MMP-2). Coinfusion of metformin (150 mg/kg/24 h) with isoproterenol partially inhibited cardiac hypertrophy that was followed by reduced IL-6, TGF-Ղ, ANP, collagen I and III, and MMP-2. Chronic subcutaneous infusion of metformin did not increase AMP-activated protein kinase (AMPK) activity in heart, although acute intraperitoneal injection of metformin (10 mg/kg) increased AMPK activity. Isoproterenol increased nitrotyrosine levels and mRNA expression of antioxidant enzyme glutathione peroxidase and metformin treatment normalized these changes. These results suggest that metformin inhibits cardiac hypertrophy through attenuating oxidative stress.