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.


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.
Young
L H
LH
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520-8017, USA. lawrence.young@quickmail.yale.edu
Renfu
Y
Y
Russell
R
R
Hu
X
X
Caplan
M
M
Ren
J
J
Shulman
G I
GI
Sinusas
A J
AJ
D000818:Animals; D001692:Biological Transport; D004285:Dogs; D005455:Fluorescent Antibody Technique; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D006321:Heart / Q000503:physiopathology; D007425:Intracellular Membranes / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009124:Muscle Proteins; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D012039:Regional Blood Flow; D012508:Sarcolemma / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D014018:Tissue Distribution
D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins