Key result
Reduction of cardiac GLUT4 levels to less than 5% of normal resulted in marked cardiac hypertrophy, whereas 15% of normal levels was sufficient to maintain insulin-stimulated glucose uptake.
Why the study?
Does a reduction in GLUT4 levels impair cardiac glucose uptake and cause cardiac hypertrophy in mice?
Does a reduction in GLUT4 levels impair cardiac glucose uptake and cause cardiac hypertrophy in mice?
Absolute Event Rate: 8.2% vs 5.5%
p-value: p=<0.01
A very low threshold of GLUT4 expression (5% of normal) is sufficient to maintain insulin-stimulated glucose uptake and prevent cardiac hypertrophy in mice.
Threshold GLUT4 levels prevent hypertrophy in mice; hypothesis-generating for human cardiac metabolism studies.
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.
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Kaczmarczyk et al. (2003) studied Cardiac hypertrophy. Profound GLUT4 deficiency (Lox+/+Cre+/- mice) vs. Partial GLUT4 deficiency (Lox+/+ mice) and Wild-type mice was evaluated on Heart weight to body weight ratio (HW/BW, mg/g) (p=<0.01). Reduction of cardiac GLUT4 levels to less than 5% of normal resulted in marked cardiac hypertrophy, whereas 15% of normal levels was sufficient to maintain insulin-stimulated glucose uptake.
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