Downregulation of peroxisme proliferator activated receptor gamma co-activator 1a in diabetic rats -: Role of pharmacomodulation

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 1 alpha (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-1 alpha 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-1 alpha in the left ventricular myocardium. These rats were divided into group I (insulin therapy only, n = 8), group II (insulin plus sitrivastatin 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-1 alpha was measured using real-time polymerase chain reaction (RT-PCR). Additionally, transthoracic echocardiography was performed on days 0 and 2 1. The experimental results indicated that the mRNA expression of PGC-1 alpha and the left ventrictilar 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-1 alpha and the LVEF were significantly higher in group III than in groups I and II (both P < 0.01). Conversely, mRNA expression of PGC-1 alpha and LVEF did not differ between groups I and II (P > 0.5). In conclusion, DM induces suppression of mRNA expression of PGC-1 alpha and LV function in diabetic rats. Losartan and not sinivastatin therapy improved the LV function and the expression of this mitochondrial-biogenesis regulator.