Uteroplacental insufficiency causes
intrauterine growth retardation (IUGR) and subsequent low birth weight, which predisposes the affected newborn towards
adult Syndrome X. Individuals with Syndrome X suffer increased morbidity from adult
ischemic heart disease.
Myocardial ischemia initiates a defensive increase in cardiac
glucose metabolism, and individuals with Syndrome X demonstrate reduced
insulin sensitivity and reduced
glucose uptake.
Glucose transporters GLUT1 and GLUT4 facilitate
glucose uptake across cardiac plasma membranes, and
hexokinase II (HKII) is the predominant
hexokinase isoform in adult cardiac tissue. We therefore hypothesized that GLUT1, GLUT4 and HKII gene expression would be reduced in heart muscle of growth-retarded rats, and that reduced gene expression would result in reduced myocardial
glucose uptake. To prove this hypothesis, we measured cardiac GLUT1 and GLUT4
mRNA and
protein in control IUGR rat hearts at day 21 and at day 120 of life. HKII
mRNA quantification and 2-deoxyglucose-uptake studies were performed in day-120 control and IUGR cardiac muscle. Both GLUT1 and GLUT4
mRNA and
protein were significantly reduced at day 21 and at day 120 of life in IUGR hearts. HKII
mRNA was also reduced at day 120. Similarly, both basal and
insulin-stimulated
glucose uptake were significantly reduced in day-120 IUGR cardiac muscle. We conclude that adult rats showing IUGR as a result of uteroplacental insufficiency express significantly less cardiac GLUT1 and GLUT4
mRNA and
protein than control animals (which underwent
sham operations), and that this decrease in gene expression occurs in parallel with reduced myocardial
glucose uptake. We speculate that this reduced GLUT gene expression and
glucose uptake contribute towards mortality from
ischemic heart disease seen in adults born with IUGR.