The influence of diabetes on cardiac β-adrenoceptor subtypes

Abstract

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.

Maternal hyperglycemia leads to fetal cardiac hyperplasia and dysfunction in a rat model

“…Cardiac function and left ventricular pressure characteristics were comparable with those of healthy control mice at baseline conditions, but the inotropic and lusitropic responses to dobutamine stress test were attenuated in adult type 2 diabetic mice (8). Downregulation of adrenoceptor-␤1 induced by diabetes was speculated to cause these cardiovascular changes (1). However, in our study, fetal Adrb1 expression was not affected by maternal hyperglycemia and is thus unlikely to contribute to the observed reduction in FHR.…”

The Effect of Long-Term Intranasal Serotonin Treatment on Metabolic Parameters and Hormonal Signaling in Rats with High-Fat Diet/Low-Dose Streptozotocin-Induced Type 2 Diabetes

“…Many neurotransmitters and neurohormones also exert regulatory effects on the biochemical and physiological processes in the CNS and in the periphery via ACSS. It was shown by us and the other authors that the changes in ACSS activity in diabetic tissues correlate positively with severity and duration of DM2 [30–36]. Therefore, the study of ACSS is one of the most promising approaches to be used in the case of DM2 for identification of functional abnormalities in the CNS and the periphery as well as for monitoring dysfunctions in the nervous, cardiovascular, and other systems and for evaluation of the effectiveness of antidiabetic therapy [13, 31, 32, 37].…”

“…An important role in the etiology and pathogenesis of DM2 and its complications is assigned to alterations in the brain and peripheral hormonal signaling systems, the hormone-sensitive adenylyl cyclase signaling system (ACSS) in particular [30–32]. The ACSS plays a key role in the regulation of contractile function of the heart by adrenergic agonists.…”

Alterations of Hormone-Sensitive Adenylyl Cyclase System in the Tissues of Rats with Long-Term Streptozotocin Diabetes and the Influence of Intranasal Insulin

“…One of the causes of these complications is the alterations in hormone-sensitive signaling systems, the adenylyl cyclase (AC) system in particular [3,4]. It was shown that changes in the functional activity of AC system in the heart, brain, and reproductive tissues in experimental T1DM were tissue and hormone speci�c [5][6][7][8][9][10].…”