Diyabet kaynaklı kalp fonksiyon bozukluğunda hücre içi iyon derişimleri ile fosfodiesterazların aktiviteleri arasındaki ilişkinin tip 2 obez-sıçan modelinde incelenmesi
Metabolic syndrome (MetS) is a disease characterized by obesity, hyperinsulinemia, hyperlipidemia, hypertension and an important risk factor for development of type-2 diabetes and cardiovascular diseases. Previous studies reported that hyperglycemia, hyperlipidemia, insulin resistance, hypertension and cardiac dysfunction in high-sucrose diet induced MetS disease model. In light of these data, in this study we attempted to investigate the underlying mechanisms of MetS-induced cardiac dysfunction and the effects of phosphodiesterases (PDEs) on the pathophysiology. We found that MetS induced cardiac dysfunction through myofibril loss, connective tissue and lipid accumulation in the myocardium and alterations of Ca2+ handling protein activities. Cardiac expressions and activities of PDEs increased in MetS and, consistent with these results, the effects of PDE inhibitors on the pathways that control cardiac contraction were higher than those in the control group. In conclusion, we established that a 16-wk high sucrose feeding protocol, which induced cardiac dysfunction, leads to MetS disease model in rats. We define the components of MetS-induced cardiac dysfunction as follows: structural changes in myocardium, Ca2+ dyshomeostasis and increased PDE activity. The most striking result of this study is, in the absence of type-2 diabetes or obesity, MetS induced by a high-sucrose diet was enough to alter cardiac performance in the rats. The presence of insulin resistance or MetS should be taken into account in connection with the clinical use of the PDE inhibitors to avoid their potential side effects.