title: Regulation of cardiac β3-adrenergic receptors in hyperglycemia.
abstract: Beta-adrenoceptors (β-AR), members of the G protein-coupled receptors play important roles in the regulation of heart function. A positive inotropic action of catecholamines is mediated through their interaction with β-AR, located on the sarcolemma, while they can also mediate some deleterious effects, such as cardiac arrhythmias or myocardial apoptosis. The well-known β-AR-associated signaling in heart is composed of a coupled mechanism among both β1- and β2-AR and stimulatory G protein (G(s)). 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 G(i) proteins, thereby initiating additional signal transduction pathways, particularly under physiopathological conditions. 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 appear to involve a pertussis toxin (PTX)-sensitive G protein and the activation of a nitric oxide synthase pathway. On the other hand, β-blockers demonstrate marked beneficial effects in heart dysfunction with scavenging free radicals and/or acting as an antioxidant with both sex- and dose-dependent manner. However, further investigations are needed to clarify the roles of both altered expression and/or responsiveness of β-AR and the benefits with β-blocker treatment in diabetes. This review discusses the role of β-AR activation, particularly β3-AR in cardiac pathological remodeling under hyperglycemia.
authors.forename: Belma
authors.initials: B
authors.lastname: Turan
authors.forename: Erkan
authors.initials: E
authors.lastname: Tuncay
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000276:immunology*; D048909:Diabetes Complications / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D006943:Hyperglycemia / Q000276:immunology*; D008955:Models, Cardiovascular; D018448:Models, Immunological; D009206:Myocardium / Q000276:immunology*; D022702:Receptors, Adrenergic, beta-3 / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D022702:Receptors, Adrenergic, beta-3