Abstract P307: A Novel Protective Effect of the Antidiabetic Drug Voglibose via GLP-1 Receptor in the Infarcted Heart

Abstract

Glucagon-like peptide 1 (GLP-1) reportedly exerts a protective effect against cardiac ischemia. We hypothesized that the α-glucosidase inhibitor voglibose, an unabsorbable antidiabetic drug with cardioprotective effects, may act via stimulation of GLP-1 receptors. The results of the present study suggest oral administration of voglibose reduces myocardial infarct size and mitigates cardiac dysfunction in rabbits following 30 min of coronary occlusion and 48 h of reperfusion. Voglibose increased basal and postprandial plasma GLP-1 levels and reduced postprandial plasma glucose levels. The infarct size-reducing effect of voglibose was abolished by treatment with exendin(9–39), wortmannin, L-NAME or 5-HD, which inhibit GLP-1 receptors, PI3K, NOS and K ATP channels, respectively. Western blot analysis showed that treatment with voglibose upregulated myocardial expression of phospho-Akt, phospho-eNOS, phospho-ERK and HSP27 following myocardial infarction. The upregulation of phospho-Akt was inhibited by exendin(9–39) and wortmannin, while the upregulation of phospho-ERK and HSP27 was inhibited by wortmannin but not by exendin(9–39). These findings suggest that voglibose reduces myocardial infarct size through stimulation of GLP-1 receptors, activation of PI3K-Akt-eNOS and ERK pathways, and the opening of mitochondrial K ATP channels. These findings may provide new insight into therapeutic strategies for the treatment of diabetic patients with coronary artery disease.