LOW-FLOW ISCHEMIA LEADS TO TRANSLOCATION OF CANINE HEART GLUT-4 AND GLUT-1 GLUCOSE TRANSPORTERS TO THE SARCOLEMMA IN-VIVO

Background Myocardial ischemia increases heart glucose utilization in vivo. However, whether low-flow ischemia leads to the translocation of glucose transporter (GLUT)-4 and/or GLUT-1 to the sarcolemma in vivo is unknown. Methods and Results In a canine model, we evaluated myocar dial glucose metabolism in vivo and the distribution of GLUT-4 and GLU T-I by use of immunoblotting of sarcolemma and intracellular membranes and immunofluorescence localization with confocal microscopy. In vivo glucose extraction increased fivefold (P<.001) and was associated wit h net lactate release in the ischemic region. Ischemia led to an incre ase in the sarcolemma content of both GLUT-4 (15+/-2% to 30+/-3%, P<.0 2) and GLUT-1 (41+/-4% to 58+/-3%, P<.03) compared with the nonischemi c region and to a parallel decrease in their intracellular contents. I mmunofluorescence demonstrated the presence of both GLUT-4 and GLUT-1 on cardiac myocytes. GLUT-1 had a more prominent cell surface pattern than GLUT-4, which was primarily intracellular in the nonischemic regi on. However, significant GLUT-4 surface labeling: was found in the isc hemic region. Conclusions Translocation of the insulin-responsive GLUT -4 transporter from an intracellular storage pool to the sarcolemma oc curs in vivo during acute low-flow ischemia. GLUT-1 is also present in an intracellular storage pool from which it undergoes translocation t o the sarcolemma in response to ischemia. These results indicate that both GLUT-1 and GLUT-4 are important in ischemia-mediated myocardial g lucose uptake in vivo.