Abstract 3888: Voglibose, an α-Glucosidase Inhibitor, Reduces Myocardial Infarct Size and Improves Left Ventricular Function via Stimulation of GLP-1 Receptors and PI3 Kinase-Akt-eNOS Pathway in Rabbits
Glucagon-Like Peptide-1(GLP-1) has been reported to prevent postprandial hyperglycemia and to protect the heart. We hypothesized that an α-glucosidase inhibitor voglibose might reduce myocardial infarct size via production of GLP-1. Japanese white rabbits underwent 30 min of coronary occlusion followed by 48 h of reperfusion. Rabbits were assigned randomly to 6 groups (n=7 in each): a control group, a voglibose group fed diets containing 0.05 mg/kg/day voglibose for 7days, and a voglibose + exendin (9 –39) group (fed the same diet as the voglibose group along with i.v. exendin (9 –39), a GLP-1 receptor blocker, 3 nmol/l), an exendin only (9 –39) group (3 nmol/l ), a voglibose + wortmannin group (fed the same diet as the voglibose group along with i.v. wortmannin, a PI3K inhibitor 0.6mg/kg), a wortmannin only group (0.6mg/kg). Myocardial infarct size was measured as a percentage of the risk area. Cardiac function was evaluated by echocardiography. Plasma GLP-1 levels were measured before and 1, 2 and 3 hours after eating. Western blotting was performed to examine the expression of Akt and eNOS in the myocardium. The infarct size was significantly smaller in the voglibose group (23.4±3.0%) than in the control group (43.8±3.4%) (p<0.001), and this effect was abolished by pretreatment with exendin(9 –39) (38.2 ±2.9 %) or wortmannin (46.8±1.8% ). By itself, exendin(9 –39) (40.6±4.7 %) or wortmannin (41.8 ±3.2 %) had no effect on infarct size. Ejection fraction in the voglibose group (65.4±1.6%) was significantly larger than that in the control group (54.9±2.5%) (p<0.001). This effect was completely abolished by exendin(9 –39) (53.4±1.2%) or wortmannin (50.0±2.6% ), though, by itself, exendin(9 –39) (54.5±0.9%) and wortmannin (49.6±1.0%) had no effect on ejection fraction .Voglibose increased plasma GLP-1 levels. Phospho-Akt and phospho-eNOS were over-expressed in the myocardium of the voglibose group. The α-glucosidase inhibitor voglibose reduces myocardial infarct size and improves left ventricular function via stimulation of GLP-1 receptors and PI3-kinase, Akt and eNOS in rabbits. This finding may provide new insight into therapeutic strategies for diabetic patients with coronary artery disease.