(Circulation. 1997;95:415-422.)
© 1997 American Heart Association, Inc.
Articles |
Low-Flow Ischemia Leads to Translocation of Canine Heart GLUT-4 and GLUT-1 Glucose Transporters to the Sarcolemma In Vivo
the Department of Internal Medicine, Yale University School of Medicine, New Haven; the Department of Physiology, Yale University School of Medicine (M.C.), New Haven; and Bayer Metabolic Disorders Research Division (J.R.), West Haven, Conn.
Correspondence to Lawrence H. Young, MD, Section of Cardiovascular Medicine, Yale University School of Medicine, 333 Cedar St, FMP 323, New Haven, CT 06520-8017. E-mail lawrence.young{at}quickmail.yale.edu
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 myocardial glucose metabolism in vivo and the distribution of GLUT-4 and GLUT-1 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 with net lactate release in the ischemic region. Ischemia led to an increase in the sarcolemma content of both GLUT-4 (15±2% to 30±3%, P<.02) and GLUT-1 (41±4% to 58±3%, P<.03) compared with the nonischemic region and to a parallel decrease in their intracellular contents. Immunofluorescence 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 region. However, significant GLUT-4 surface labeling was found in the ischemic region.
Conclusions Translocation of the insulin-responsive GLUT-4 transporter from an intracellular storage pool to the sarcolemma occurs in vivo during acute low-flow ischemia. GLUT-1 is also present in an intracellular storage pool from which it undergoes translocation to the sarcolemma in response to ischemia. These results indicate that both GLUT-1 and GLUT-4 are important in ischemia-mediated myocardial glucose uptake in vivo.
Key Words: glucose • ischemia • metabolism • immunohistochemistry • endocardium
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