Protective effects of glucagon-like peptide-1 on cardiac remodeling by inhibiting oxidative stress through mammalian target of rapamycin complex 1/p70 ribosomal protein S6 kinase pathway in diabetes mellitus

Abstract

Aims/introduction: Although increased reactive oxygen species (ROS) generation is a major mechanism leading to cardiac remodeling in diabetes mellitus, research into the effects of anti-oxidation on diabetic cardiac remodeling remains scarce and controversial. Glucagon-like peptide-1 (GLP-1) shows potential anti-oxidative effects besides lowering blood glucose. The objective of this research was to investigate the effects of GLP-1 on cardiac remodeling and the molecular mechanism involved in diabetes mellitus.

Materials and methods: Streptozotocin-induced diabetic rats received exenatide treatment for 3 months. Cardiac function, cardiac weight index and myocardial interstitial fibrosis were measured. Cardiomyocytes were cultured in high-glucose medium with GLP-1 treatment. The ROS production, apoptosis and the levels of mammalian target of rapamycin complex 1/p70 ribosomal protein S6 kinase protein expression in cardiomyocytes were analyzed.

Results: Experimental diabetes mellitus showed impaired cardiac diastolic function, increased brain natriuretic peptide expression and increased interstitial collagen deposition in the myocardium, which were ameliorated by exenatide treatment. Exenatide reduced myocardial ROS production and apoptosis in diabetes mellitus. Also, high glucose-induced ROS generation and apoptosis in cardiomyocytes were inhibited by GLP-1, as well as the levels of mammalian target of rapamycin complex 1/p70 ribosomal protein S6 kinase phosphorylation. Furthermore, GLP-1 treatment upregulated adenosine monophosphate-activated protein kinase activity in high-glucose-induced cardiomyocyte.

Conclusions: Glucagon-like peptide-1 protects the cardiomyocytes from oxidative stress and apoptosis in diabetes mellitus, which might contribute to the improvement of cardiac remodeling. The cardiac protection of GLP-1 might be dependent on inhibition of mammalian target of rapamycin complex 1/p70 ribosomal protein S6 kinase, through an adenosine monophosphate-activated protein kinase-mediated pathway.

Keywords: Cardiac remodeling; Diabetes mellitus; Glucagon-like peptide-1.