Esma Nur Okatan and Belma Turan
Cumhuriyet University, Turkey
Ankara University, Turkey
Posters & Accepted Abstracts: J Diabetes Metab
Phosphodiesterases (PDEs) play an important role in modulation of cardiac contractility through the degradation of cyclic nucleotides. It has been shown that altered PDE activity induces obesity, insulin resistance, hypertension as well as cardiovascular diseases. PDE inhibitors have inotropic and lusiotropic effects on cardiomyocytes by modulating L-type Ca2+ channels (LTCC), ryanodine receptors (RyR2), sarcoplasmic reticulum Ca2+ load and myo-filament Ca2+sensitivity. The proposed mechanism for the effects is increased activity of protein kinase-A mediated protein phosphorylation. While PDEs-inhibitors have acute inotropic effects on the heart, chronic use of the drugs leads to heart failure and arrhythmias. Studies have been designed to understand the mechanisms underlying these effects. Recent studies show that PDEs are specifically located nearby key contractility modulators such as RyR2, LTCC and SERCA. This micro-domain specific function has to be taken into consideration in evaluating the effects of PDEs-inhibitors on the heart. Although several studies have explored cardiac PDE activity, only few studies investigated the role of cardiac PDE activity in obesity. Therefore, we investigated the role of PDE activity in the heart from high sucrose-induced metabolic syndrome (Met S) developed overweight-rats. Our data showed important levels of increased protein expression and activity in both PDE3 and PDE4, which seem to play an important role in the development of cardiac dysfunction in insulin resistant overweight-rats. In conclusion, the use of PDEs-inhibitors seems to have beneficial actions in the treatment of Met S-associated heart diseases, while it needs further studies on selectively target PDE subtypes or micro-domains under these types of pathological conditions.
