Ischemia induces translocation of the insulin-responsive glucose transporter GLUT4 to the plasma membrane of cardiac myocytes

DaQing Sun, Ngoc Nguyen, Timothy R DeGrado, Markus Schwaiger, Frank C. Brosius

Research output: Contribution to journalArticle

206 Citations (Scopus)

Abstract

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 membranes 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.

Original languageEnglish (US)
Pages (from-to)793-798
Number of pages6
JournalCirculation
Volume89
Issue number2
StatePublished - Feb 1994
Externally publishedYes

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Glucose Transporter Type 4
Cardiac Myocytes
Ischemia
Cell Membrane
Insulin
Facilitative Glucose Transport Proteins
Glucose
Myocardial Ischemia
Intracellular Membranes
Myocardium

Keywords

  • coronary disease
  • metabolism

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Ischemia induces translocation of the insulin-responsive glucose transporter GLUT4 to the plasma membrane of cardiac myocytes. / Sun, DaQing; Nguyen, Ngoc; DeGrado, Timothy R; Schwaiger, Markus; Brosius, Frank C.

In: Circulation, Vol. 89, No. 2, 02.1994, p. 793-798.

Research output: Contribution to journalArticle

Sun, DaQing ; Nguyen, Ngoc ; DeGrado, Timothy R ; Schwaiger, Markus ; Brosius, Frank C. / Ischemia induces translocation of the insulin-responsive glucose transporter GLUT4 to the plasma membrane of cardiac myocytes. In: Circulation. 1994 ; Vol. 89, No. 2. pp. 793-798.
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AB - 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 membranes 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.

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