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Cellular and molecular life sciences : CMLS
Aug, 2011;68 (15): 2525-38.

Subcellular trafficking of the substrate transporters GLUT4 and CD36 in cardiomyocytes.

Laura K M Steinbusch, Robert W Schwenk, D Margriet Ouwens, Michaela Diamant, Jan F C Glatz, Joost J F P Luiken
Author Information
  1. Laura K M Steinbusch: Department of Molecular Genetics, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands. laura.steinbusch@maastrichtuniversity.nl
PMID: 21547502 DOI: 10.1007/s00018-011-0690-x

Abstract

Cardiomyocytes use glucose as well as fatty acids for ATP production. These substrates are transported into the cell by glucose transporter 4 (GLUT4) and the fatty acid transporter CD36. Besides being located at the sarcolemma, GLUT4 and CD36 are stored in intracellular compartments. Raised plasma insulin concentrations and increased cardiac work will stimulate GLUT4 as well as CD36 to translocate to the sarcolemma. As so far studied, signaling pathways that regulate GLUT4 translocation similarly affect CD36 translocation. During the development of insulin resistance and type 2 diabetes, CD36 becomes permanently localized at the sarcolemma, whereas GLUT4 internalizes. This juxtaposed positioning of GLUT4 and CD36 is important for aberrant substrate uptake in the diabetic heart: chronically increased fatty acid uptake at the expense of glucose. To explain the differences in subcellular localization of GLUT4 and CD36 in type 2 diabetes, recent research has focused on the role of proteins involved in trafficking of cargo between subcellular compartments. Several of these proteins appear to be similarly involved in both GLUT4 and CD36 translocation. Others, however, have different roles in either GLUT4 or CD36 translocation. These trafficking components, which are differently involved in GLUT4 or CD36 translocation, may be considered novel targets for the development of therapies to restore the imbalanced substrate utilization that occurs in obesity, insulin resistance and diabetic cardiomyopathy.

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MeSH Term

Animals
CD36 Antigens
Fatty Acids
Glucose
Glucose Transporter Type 4
Humans
Intracellular Space
Models, Biological
Myocytes, Cardiac
Protein Transport

Chemicals

CD36 Antigens
Fatty Acids
Glucose Transporter Type 4
Glucose
Journal Article Research Support, Non-U.S. Gov't Review

Word Cloud

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