The influence of diabetes on cardiac β-adrenoceptor subtypes

Despite the significant developments in the treatment of diabetes mellitus, diabetic patients still continue to suffer from cardiac complications. The increase of cardiac adrenergic drive may ultimately contribute to the development and progression of diabetic cardiomyopathy. beta-Adrenoceptors play an important role in the regulation of heart function. However, responsiveness of diabetic heart to beta-adrenoceptor agonist stimulation is diminished. The chronotropic responses mediated by beta(1)-subtype, which is mainly responsible for cardiac effects of catecholamines are decreased in the atria of diabetic rats. The expression of cardiac beta(1)-subtype is significantly decreased in diabetic rats as well. beta(2)-Adrenoceptors also increase cardiac function. Although the expression of this subtype is slightly decreased in diabetic rat hearts, beta(2)-mediated chronotropic responses are preserved. On the other hand, functional beta(3)-adrenoceptor subtype was characterized in human heart. Interestingly, stimulation of cardiac beta(3)-adrenoceptors, on the contrary of beta(1)- and beta(2)-subtypes, mediates negative inotropic effect in human ventricular muscle. Cardiac beta(3)-adrenoceptors are upregulated in experimental diabetes as well as in human heart failure. These findings suggest that each beta-adrenoceptor subtype may play an important role in the pathophysiology of diabetes-induced heart disease. However, it is still not known whether the changes in the expression and/or responsiveness of beta-adrenoceptors are adaptive or maladaptive. Therefore, this review outlines the potential roles of these receptor subtypes in cardiac pathologies of diabetes.