Low-flow ischemia leads to translocation of canine heart GLUT-4 and GLUT-1 glucose transporters to the sarcolemma in vivo

Circulation. 1997 Jan 21;95(2):415-22. doi: 10.1161/01.cir.95.2.415.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biological Transport
  • Dogs
  • Fluorescent Antibody Technique
  • Glucose Transporter Type 1
  • Glucose Transporter Type 4
  • Heart / physiopathology
  • Intracellular Membranes / metabolism
  • Monosaccharide Transport Proteins / metabolism*
  • Muscle Proteins*
  • Myocardial Ischemia / metabolism*
  • Myocardial Ischemia / pathology
  • Myocardial Ischemia / physiopathology*
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Regional Blood Flow
  • Sarcolemma / metabolism*
  • Subcellular Fractions / metabolism
  • Tissue Distribution

Substances

  • Glucose Transporter Type 1
  • Glucose Transporter Type 4
  • Monosaccharide Transport Proteins
  • Muscle Proteins