Circulation, Vol 89, 793-798, Copyright © 1994 by American Heart Association
D Sun, N Nguyen, TR DeGrado, M Schwaiger and FC Brosius 3rd
BACKGROUND: Acute myocardial ischemia is accompanied by an increase in
glucose uptake and metabolism, which appears to be important in protecting
myocardial cells from irreversible ischemic injury. Because insulin
augments myocardial glucose uptake by inducing the translocation of glucose
transporters from an intracellular compartment to the plasma membrane, we
hypothesized that acute ischemia would trigger a similar translocation.
METHODS AND RESULTS: We used a subcellular fractionation method to separate
intracellular membrane and plasma membranes from control, ischemic, and
hypoxic Langendorff- isolated perfused rat hearts and determined the
expression of the major myocardial glucose transporter, GLUT4, in these
separated membrane fractions. We found that translocation of GLUT4
molecules occurred in ischemic, hypoxic, and insulin-treated hearts and in
hearts that underwent ischemia plus insulin treatment. The percentages of
GLUT4 molecules present on the plasma membrane in the different conditions
were as follows: control, 18.0 +/- 2.8%; ischemia, 41.3 +/- 9.4%; hypoxia,
31.1 +/- 2.9%; insulin, 61.1 +/- 2.6%; and ischemia plus insulin, 66.8 +/-
5.7%. Among the statistically significant differences in these values were
the difference between control and ischemia and the difference between
ischemia alone and insulin plus ischemia. CONCLUSIONS: Ischemia causes
substantial translocation of GLUT4 molecules to the plasma membrane of
cardiac myocytes. A combination of insulin plus ischemia stimulates an even
greater degree of GLUT4 translocation. GLUT4 translocation is likely to
mediate at least part of the increased glucose uptake of ischemic
myocardium and may be a mechanism for the cardioprotective effect of
insulin during acute myocardial ischemia.
ARTICLES
Ischemia induces translocation of the insulin-responsive glucose transporter GLUT4 to the plasma membrane of cardiac myocytes
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor.
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