Abstract 1114: The Role of Myocardial Glut4 in Ischemia-Reperfusion Injury
Background: Mice with global ablation of glucose transporter-4 (Glut4−/−) are insulin resistant, have normal cardiac glucose uptake, increased glycogen synthesis, decreased expression of fatty acid enzymes and increased heart weight. Cardiac specific re-expression of Glut4 into Glut4−/−(Glut4−/−CS-Tg) normalizes heart weight but not peripheral insulin resistance. This model system was used to evaluate the role of cardiac Glut4 in myocardial ischemia-reperfusion (MI-R).
Methods: Glut4−/−, Glut4−/−CS-Tg, and wild-type (WT) mice were subjected to 30 min of coronary artery occlusion and 72 hr R in vivo. High-resolution echocardiography was performed at baseline and 72 hr of R and infarct size was determined at 72 hr of R.
Results: Glut4−/− mice exhibited a 19% reduction in infarct size per area-at-risk compared to all other groups (p = NS). At baseline, Glut4−/−mice exhibited a dilated, hypertrophic phenotype. MI exacerbated this phenotype as evidenced by a mean percent fractional shortening of 14%. The decreased function and severe LV dilatation seen post-MI in Glut4−/− mice was restored to WT levels in Glut4−/−CS-Tg mice. Glut4−/− mice were also found to have significantly decreased survival post-MI compared to all other groups.
Conclusions: Ablation of cardiac Glut4 does not significantly protect against MI-R injury. The dilated, hypertrophic cardiac phenotype found at baseline in the Glut4−/− is exacerbated following MI-R injury. Reconstitution of Glut4 into hearts of Glut4−/− restores function to that of WT. Future studies are needed to elucidate the mechanisms responsible for impaired cardiac structure and function resulting from myocardial Glut4 deficiency.