Abstract 3213: Acarbose, an α -glucosidase Inhibitor, Reduces Myocardial Infarct Size in Rabbits via Stimulation of GLP-1 Receptors, Opening Mitochondrial KATP Channels, and Preventing Hydroxyl Radical Production

Abstract

Background: Acarbose, an anti-diabetic drug, is an α– glucosidase inhibitor that can inhibit glucose absorption in the intestine. A recent large-scale clinical trial, STOP-NIDDM, showed that acarbose reduces the risk of myocardial infarction. We examined whether acarbose reduces myocardial infarct size and investigated its mechanisms. Methods and Results: Rabbits were fed with one of four diets in this study: normal chow, 30 mg acarbose/100 g chow, 8 g sucrose/100 g chow, or 30 mg acarbose plus 8 g sucrose/100 g chow for 7 days. Rabbits were assigned randomly to one of eight groups: control (n=10), acarbose (n=10), sucrose (n=10), acarbose+sucrose (n=10), acarbose+i.v. 5-hydroxydecanoate (5HD, a mitochondrial KATP channel blocker, 5 mg/kg) (n=10), 5HD (i.v. 5 mg/kg, n=10), acarbose+exendin(9 –39) (n=10, a Glucagon-Like Peptide-1(GLP-1) receptor blocker, 3 nmol/l) (45.4±1.2%) and exendin(9 –39)(n=10). Rabbits then underwent 30 min of coronary occlusion followed by 48 h reperfusion. Postprandial blood glucose levels were highest in the sucrose group and higher in the control groups, but decreased in the acarbose and sucrose+acarbose groups. The infarct size as a percentage of the left ventricular area at risk was reduced significantly in the acarbose (19.4±2.3%) and sucrose+acarbose groups (19.0±5.6%) as compared with the sucrose (47.4±4.2%) and control groups (42.8±5.4%). The infarct size-reducing effect of acarbose was abolished by 5HD (43.4±4.7%) and exendin(9 –39) (45.4±1.2%). The 5HD and exendin(9 –39) by itself did not affect the infarct size. Myocardial interstitial 2,5-DHBA levels, an indicator of hydroxyl radicals, increased during reperfusion after 30 min of ischemia but this increase was inhibited in the acarbose group. Conclusions: Acarbose reduces myocardial infarct size via stimulation of GLP-1 receptors, opening mitochondrial KATP channels, and preventing hydroxyl radical production.