Responses of GLUT4-deficient hearts to ischemia underscore the importance of glycolysis

R Tian; E D Abel

doi:10.1161/01.CIR.103.24.2961

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Responses of GLUT4-deficient hearts to ischemia underscore the importance of glycolysis

Journal article

Open access

Peer reviewed

Responses of GLUT4-deficient hearts to ischemia underscore the importance of glycolysis

R Tian and E D Abel

Circulation (New York, N.Y.), Vol.103(24), pp.2961-2966

06/19/2001

DOI: 10.1161/01.CIR.103.24.2961

PMID: 11413087

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Abstract

The ischemic heart is dependent on glycolysis for ATP generation, and therapies that increase glucose utilization during ischemia improve survival. Myocardial ischemia results in the translocation of the glucose transporter proteins GLUT1 and GLUT4 to the sarcolemma. The increased glucose entry via these transporters contributes to enhanced glycolysis during ischemia. To determine the role of GLUT4 in mediating increased glycolytic flux during ischemia, hearts from mice with cardiac-selective GLUT4 deficiency (G4H-/-) were subjected to global low-flow ischemia. During normal perfusion, hearts from fed G4H-/- mice showed increased GLUT1-mediated glucose uptake, higher concentrations of glycogen and phosphocreatine, but delayed recovery after ischemia. When these compensatory changes were eliminated by a 20-hour fast, G4H-/- hearts exhibited depressed glucose utilization during ischemia and developed profound and irreversible systolic and diastolic dysfunction associated with accelerated ATP depletion during ischemia and diminished regeneration of high-energy phosphate compounds on reperfusion. GLUT4 is an important mediator of enhanced glycolysis during ischemia and represents an important protective mechanism against ischemic injury.

Blood Pressure

Myocardial Ischemia - genetics

Myocardial Ischemia - metabolism

Monosaccharide Transport Proteins - deficiency

Muscle Proteins

Glycogen - metabolism

Adenosine Triphosphate - metabolism

Myocardium - metabolism

Creatine - metabolism

Lactic Acid - biosynthesis

Fasting - metabolism

Monosaccharide Transport Proteins - metabolism

Monosaccharide Transport Proteins - genetics

Myocardial Contraction

Heart Rate

Insulin - pharmacology

Glucose Transporter Type 4

Magnetic Resonance Spectroscopy

Glucose Transporter Type 1

Phosphates - metabolism

Animals

Myocardial Reperfusion

Glucose - pharmacokinetics

Glucose - metabolism

Glycolysis

Heart - drug effects

Mice

Phosphocreatine - metabolism

In Vitro Techniques

Details

Title: Subtitle: Responses of GLUT4-deficient hearts to ischemia underscore the importance of glycolysis
Creators: R Tian - NMR Laboratory for Physiological Chemistry, Division of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
E D Abel
Resource Type: Journal article
Publication Details: Circulation (New York, N.Y.), Vol.103(24), pp.2961-2966
DOI: 10.1161/01.CIR.103.24.2961
PMID: 11413087
NLM abbreviation: Circulation
ISSN: 0009-7322
eISSN: 1524-4539
Publisher: Lippincott Williams & Wilkins; United States
Grant note: P30-DK-46200 / NIDDK NIH HHS HL-62886 / NHLBI NIH HHS DK-02495 / NIDDK NIH HHS HL-59246 / NHLBI NIH HHS AG-00837 / NIA NIH HHS
Language: English
Date published: 06/19/2001
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984024540902771

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