title: Threshold effects of glucose transporter-4 (GLUT4) deficiency on cardiac glucose uptake and development of hypertrophy.
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-(14)C]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.
authors.affiliation: University of Melbourne, Department of Medicine, The Royal Melbourne Hospital, Parkville, VIC 3050, Australia.
authors.forename: S J
authors.initials: SJ
authors.lastname: Kaczmarczyk
authors.forename: S
authors.initials: S
authors.lastname: Andrikopoulos
authors.forename: J
authors.initials: J
authors.lastname: Favaloro
authors.forename: A A
authors.initials: AA
authors.lastname: Domenighetti
authors.forename: A
authors.initials: A
authors.lastname: Dunn
authors.forename: M
authors.initials: M
authors.lastname: Ernst
authors.forename: D
authors.initials: D
authors.lastname: Grail
authors.forename: M
authors.initials: M
authors.lastname: Fodero-Tavoletti
authors.forename: C E
authors.initials: CE
authors.lastname: Huggins
authors.forename: L M
authors.initials: LM
authors.lastname: Delbridge
authors.forename: J D
authors.initials: JD
authors.lastname: Zajac
authors.forename: J
authors.initials: J
authors.lastname: Proietto
mesh_terms: D000818:Animals; D001795:Blood Pressure Determination; D006332:Cardiomegaly / Q000378:metabolism / Q000503:physiopathology*; D003001:Cloning, Molecular; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology
chemical_list: D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495693:Slc2a4 protein, mouse; D005947:Glucose