Regulation of Cardiac β3-Adrenergic Receptors in Hyperglycemia.

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 (Gs). 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. 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.

Correlation of pretransplant hyperglycemia and delayed graft function in kidney transplantation

Hyperglycemia is common and a contributing factor to the undesirable outcomes in kidney transplant recipients. This study investigates the relationship of pretransplant blood glucose levels and the occurrence of delayed graft function among kidney transplant recipients without a diagnosis diabetes mellitus before transplantation. Eighty-one patients on long-term hemodialysis with no history of clinically diagnosed diabetes mellitus were enrolled in this study. Correlation of the occurrence of delayed graft function with age, gender, donor source, underlying cause of kidney failure, insulin resistance, and blood glucose levels before transplantation was evaluated. There was a significant correlation between abnormal glucose metabolism categories and occurrence of delayed graft function [P=.004]. Logistic regression analysis showed that fasting blood glucose before kidney transplantation is an independent predictor of delayed graft function immediately after transplantation [odds ratio=1.042, P=.04]. Hyperglycemic patients have an increased risk for delayed graft function and should be treated by more potent immune therapy and further restriction of blood glucose regulation in peritransplantation period