Threshold effects of glucose transporter-4 (GLUT4) deficiency on cardiac glucose uptake and development of hypertrophy

S. J. Kaczmarczyk, S. Andrikopoulos, J. Favaloro, A. A. Domenighetti, A. Dunn, M. Ernst, D. Grail, M. Fodero-Tavoletti, C. E. Huggins, L. M. Delbridge, J. D. Zajac*, J. Proietto

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

The aim of this study was to investigate the metabolic and structural consequences of a decrease in glucose transporter-4 (GLUT4) levels on the heart. The CreLoxP system was utilised to delete GLUT4 in muscle tissue including heart. The presence of the PGK-neoR cassette in the GLUT4-Lox mice resulted in reduced expression in all tissues to levels 15-30% of wild-type control mice. In mice expressing Cre recombinase, there was a further reduction of GLUT4 in cardiac tissue to almost undetectable levels. Cardiac glucose uptake was measured basally and during a euglycaemic/hyperinsulinaemic clamp using 2-deoxy-[1-14C]glucose. Insulin-stimulated glucose uptake was normal in hearts expressing 15% of normal GLUT4 levels but markedly reduced in mice with more profound reduction in GLUT4. Cardiac enlargement occurred only when GLUT4 levels were less than 5% of normal values. In heart there is a threshold level of GLUT4 above which insulin-stimulated glucose uptake is maintained. As little as 5% of normal GLUT4 levels expressed in heart is sufficient to prevent the development of cardiac hypertrophy.

Original languageEnglish (US)
Pages (from-to)449-459
Number of pages11
JournalJournal of Molecular Endocrinology
Volume31
Issue number3
DOIs
StatePublished - Dec 2003

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Fingerprint Dive into the research topics of 'Threshold effects of glucose transporter-4 (GLUT4) deficiency on cardiac glucose uptake and development of hypertrophy'. Together they form a unique fingerprint.

Cite this