Belma Turan
Ankara University, Turkey
Title: Cardiac β-adrenoceptor subtypes in diabetes: Regulation of cardiac β3-adrenergic receptors
Biography
Biography: Belma Turan
Abstract
Positive inotropic action of catecholamines is mediated through their interaction with beta-adrenergic receptors (β-ARs), while they can also mediate some deleterious effects, such as cardiac arrhythmias. The β-ARs are members of the G protein-coupled receptors and play important roles in the regulation of heart function. Cellular signaling associated with cardiac β-ARs is composed of coupled mechanism between β1-/β2-AR and Gs proteins with contribution of constitutive β3-AR coupling to Gi proteins. This coupled mechanism further leads to the activation of adenylyl cyclase, and thereby increases in intracellular cAMP level. However, recent studies have emphasized the contribution of constitutive β3-AR coupling to Gi proteins, thereby initiating additional signal transduction pathways, particularly under physiopathological conditions such as hyperglycemia. Diabetic cardiomyopathy, as a distinct entity, is recognized due to its diminished responsiveness to β1-AR agonist stimulation in the heart from diabetic rats with no important changes in the responses mediated with β2-AR. Furthermore, an upregulation of β3-AR has been shown in diabetic rat heart with a strong negative inotropic effect on left ventricular function. Experimental data provide evidences that the mechanisms for the negative inotropic effect with β3-AR activation appears to involve activation of a nitric oxide synthase pathway. On the other hand, we have shown that although insulin resistance and cardiomyopathy are developed under high-carbohydrate diet-induced metabolic syndrome (MetS), compared to type 1 diabetes, MetS-associated cardiac dysfunction seems not to be associated with any change in β3-AR system, with similar ultrastructural changes into the myocardium