The Effects of Carvedilol on Cardiac Function and the AKT/XIAP Signaling Pathway in Diabetic Cardiomyopathy Rats

Abstract

Objectives: Diabetic cardiomyopathy (DCM) is characterized by cardiac dysfunction, myocardial inflammation, interstitial fibrosis and cardiomyocytes apoptosis. The present study aimed to investigate the effects of carvedilol on cardiac function and the AKT/XIAP signaling pathway in DCM rats. Methods: Male Wistar rats were randomly divided into 3 groups: the control group, diabetic mellitus (DM) group and DM with carvedilol treatment group. DM rats were induced by streptozotocin accompanied by high energy intake. Carvedilol was orally administered at a dose of 10 mg/kg/day. After 16 weeks, the interrelated blood data were detected by biochemical analysis. Cardiac function was evaluated by echocardiography and the serum NT-proBNP level. The changes of myocardium ultrastructural and fibrosis were determined by electron microscopy and Masson's staining. Apoptotic cells were examined by TUNEL staining and interrelated proteins were measured by immunohistochemical and Western blots. Results: Rats in the DM group showed significant serum elevation of glucose, cholesterol, triglyceride, NT-proBNP, IL-1β and TNF-α, along with decreased cardiac function. Moreover, in the DM group, the levels of myocardial apoptosis and fibrosis were all increased accompanied by upregulation of caspase-3 and downregulation of phos-AKT and phos-XIAP, whereas carvedilol treatment prevented or reversed all the changes without influencing plasma levels of glucose, cholesterol and triglyceride. Conclusions: The AKT/XIAP signaling pathway may be involved in DCM. Carvedilol can improve cardiac function, possibly not only by upregulating the AKT/XIAP antiapoptotic signaling pathway and subsequently attenuating myocardial fibrosis, but also through suppressing the myocardial inflammation response.

Incaspitolide A isolated from Carpesium cernuum L. inhibits the growth of prostate cancer cells and induces apoptosis via regulation of the PI3K/Akt/xIAP pathway

“…The results of the present study demonstrated that IA could inhibit the antiapoptotic mechanism of the cells through the regulation of expression of various proteins, and the results were consistent with previous studies (35,40,41) of the PI3K/Akt/xIAP pathway. The present results highlight a potential candidate compound for the management of prostate cancer and provide a theoretical basis for the pathogenesis of prostate cancer.…”

Metabolic effects of carvedilol through β‐arrestin proteins: investigations in a streptozotocin‐induced diabetes rat model and in C2C12 myoblasts

“…The authors concluded that they were associated and involved in the pathogenesis of diabetic cardiomyopathy. The effect of carvedilol in control animals was not investigated in this study and the authors have not linked their findings with GPCR coupling or biased agonist activity of carvedilol (Zheng et al, 2017(Zheng et al, , 2019.…”

25‑OH‑PPD inhibits hypertrophy on diabetic cardiomyopathy via the PI3k/Akt/GSK‑3β signaling pathway

“…Akt exhibits distinct key roles in regulating cardiovascular functions, such as blood pressure, regulation of myocardial systolic and diastolic functions, coronary angiogenesis and atherosclerosis (37). GSK-3β is the major substrate of the Akt-GSK-3β pathway that exerts specific physiological and biochemical functions in glycogen metabolism and plays a decisive role in diabetes-induced inflammation and fibrosis (38). Previous investigations have demonstrated that the Akt-GSK-3β signaling pathway plays an important function in diabetes-induced energy metabolic dysfunction and consequently in heart hypertrophy (39,40).…”