title: Increased sarcolemmal glucose transporter abundance in myocardial ischemia.
abstract: Many clinical and laboratory studies suggest that an increase in glucose uptake and metabolism by ischemic myocardium helps protect myocardial cells from irreversible injury. We have examined whether increased sarcolemmal abundance of cardiomyocyte glucose transporters plays a role in this adaptive response. We have shown that acute myocardial ischemia in perfused rat hearts results in increased sarcolemmal abundance of the major glucose transporter, GLUT4, by causing translocation of GLUT4 molecules from an intracellular compartment to the sarcolemma. In nonischemic control hearts only 18 +/- 2.8% of GLUT4 molecules were on the sarcolemma whereas in ischemic hearts this increased to 41 +/- 9.3%. Insulin also caused translocation of GLUT4 molecules to the sarcolemma, and resulted in 61 +/- 2.6% of GLUT4 molecules on the sarcolemma. The combination of ischemia and insulin did not result in additive increases in sarcolemmal GLUT4 abundance. In more persistent or chronic ischemia, the other major myocardial glucose transporter, GLUT1, appears to play an important role. The mRNA for this transporter, which is constitutively expressed on cardiomyocyte sarcolemma, was increased 2.0-fold in regions of hibernating myocardium in humans with coronary heart disease as well as in persistently hypoxic rat neonatal cardiomyocytes in primary culture. In neither of these conditions was GLUT4 mRNA expression increased. Thus, acute myocardial ischemia increases sarcolemmal glucose transporter abundance mainly by translocating previously synthesized GLUT4 molecules from an intracellular compartment, whereas more chronic ischemia also increases GLUT1 abundance via enhanced mRNA expression. Increased GLUT1 and GLUT4 abundance may participate in the augmented glucose uptake of ischemic myocardium and therefore may help protect ischemic myocardium from irreversible injury.
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School and Ann Arbor Veterans Affairs Hospital, 48109-0676, USA.
authors.forename: F C
authors.initials: FC
authors.lastname: Brosius
authors.forename: N
authors.initials: N
authors.lastname: Nguyen
authors.forename: S
authors.initials: S
authors.lastname: Egert
authors.forename: Z
authors.initials: Z
authors.lastname: Lin
authors.forename: G M
authors.initials: GM
authors.lastname: Deeb
authors.forename: F
authors.initials: F
authors.lastname: Haas
authors.forename: M
authors.initials: M
authors.lastname: Schwaiger
authors.forename: D
authors.initials: D
authors.lastname: Sun
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D066298:In Vitro Techniques; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins; D017202:Myocardial Ischemia / Q000378:metabolism*; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000032:analysis; D012194:RNA-Directed DNA Polymerase; D051381:Rats; D012508:Sarcolemma / Q000378:metabolism*
chemical_list: D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; C495679:Slc2a1 protein, rat; C495694:Slc2a4 protein, rat; D012194:RNA-Directed DNA Polymerase; D005947:Glucose