Downregulation of peroxisme proliferator activated receptor gamma co-activator 1alpha in diabetic rats.
Diabetes mellitus (DM), which induces alterations in energy metabolism, is the leading cause of cardiovascular disease. We postulated that peroxisome proliferator activated receptor-gamma coactivator 1alpha (PGC-alpha), a transcriptional coactivator that is the primary regulator of oxidative metabolism and mitochondrial biogenesis, and cardiac function are depressive in DM and simvastatin and losartan therapy can improve the affects of DM on mRNA expression of PGC-1alpha and cardiac function. An experimental model of DM (induced by streptozocin 60 mg/kg) in adult male rats (n = 24) was used to investigate the mRNA expression of PGC-1alpha in the left ventricular myocardium. These rats were divided into group I (insulin therapy only, n = 8), group II (insulin plus simvastatin 20 mg/kg/day orally, n = 8), and group III (insulin plus losartan 20 mg/kg/day orally, n = 8). Diabetic rats and 8 healthy rats (group IV) were sacrificed at 3 weeks following DM induction. The mRNA expression of PGC-1alpha was measured using real-time polymerase chain reaction (RT-PCR). Additionally, transthoracic echocardiography was performed on days 0 and 21. The experimental results indicated that the mRNA expression of PGC-1alpha and the left ventricular ejection fraction (LVEF %) were significantly lower in groups I, II and III than in group IV (all P < 0.001). However, the mRNA expression of PGC-1alpha and the LVEF were significantly higher in group III than in groups I and II (both P < 0.01). Conversely, mRNA expression of PGC-1alpha and LVEF did not differ between groups I and II (P > 0.5). In conclusion, DM induces suppression of mRNA expression of PGC-1alpha and LV function in diabetic rats. Losartan and not simvastatin therapy improved the LV function and the expression of this mitochondrial-biogenesis regulator.
Chang
Li-Teh
LT
Basic Science, Nursing Department, Meiho Institute of Technology, Pingtung, Taiwan, R.O.C.
Sun
Cheuk-Kwan
CK
Wang
Chi-Young
CY
Youssef
Ali A
AA
Wu
Chiung-Jen
CJ
Chua
Sarah
S
Yip
Hon-Kan
HK
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D015536:Down-Regulation; D019808:Losartan / Q000494:pharmacology; D008297:Male; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000494:pharmacology; D013318:Stroke Volume; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016277:Ventricular Function, Left / Q000502:physiology
D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D019821:Simvastatin; D019808:Losartan