Faculty Collaboration Database

Myocardial gene expression of glucose transporter 1 and glucose transporter 4 in response to uteroplacental insufficiency in the rat. J Endocrinol 2001 May;169(2):373-80

Date

04/20/2001

Pubmed ID

11312153

DOI

10.1677/joe.0.1690373

Scopus ID

2-s2.0-0035002598 (requires institutional sign-in at Scopus site)   44 Citations

Abstract

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.

Author List

Tsirka AE, Gruetzmacher EM, Kelley DE, Ritov VH, Devaskar SU, Lane RH

MESH terms used to index this publication - Major topics in bold

Analysis of Variance
Animals
Animals, Newborn
Blotting, Western
Fetal Growth Retardation
Gene Expression
Glucose
Glucose Transporter Type 1
Glucose Transporter Type 4
Glycogen
Hexokinase
In Vitro Techniques
Microvascular Angina
Monosaccharide Transport Proteins
Muscle Proteins
Myocardium
Organ Size
RNA, Messenger
Rats
Rats, Sprague-Dawley
Reverse Transcriptase Polymerase Chain Reaction