Glucose transporter protein responses to selective hyperglycemia or hyperinsulinemia in fetal sheep

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology Vol. 281; no. 5; pp. 1545 - R1552
• Main Authors: Anderson, Marianne S, Flowers-Ziegler, Judy, Das, Utpala G, Hay, William W., Jr, Devaskar, Sherin U
• Format: Journal Article
• Language: English
• Published: United States 01.11.2001
• Subjects: Adipose Tissue - embryology; Adipose Tissue - metabolism; Animals; Blood Glucose - metabolism; Brain - embryology; Brain - metabolism; Female; Fetal Heart - metabolism; Fetus - metabolism; Glucose - metabolism; Glucose Transporter Type 1; Glucose Transporter Type 2; Glucose Transporter Type 3; Glucose Transporter Type 4; Hyperglycemia - metabolism; Hyperinsulinism - metabolism; Insulin - blood; Liver - embryology; Liver - metabolism; Monosaccharide Transport Proteins - metabolism; Muscle Proteins; Nerve Tissue Proteins; Pregnancy; Sheep - embryology
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.2001.281.5.r1545

1  Division of Neonatology, Department of Pediatrics, University of Colorado, Denver, Colorado 80262; 2  Division of Neonatology and Developmental Biology, Department of Pediatrics, University of Pittsburgh, Magee Womens Research Institute, Pittsburgh, Pennsylvania 15213; and 3  Division of Neonatology and Developmental Biology, Department of Pediatrics, University of California Los Angeles School of Medicine, Los Angeles, California 90095 - 1752 The acute effect of selective hyperglycemia or hyperinsulinemia on late gestation fetal ovine glucose transporter protein (GLUT-1, GLUT-3, and GLUT-4) concentrations was examined in insulin-insensitive (brain and liver) and insulin-sensitive (myocardium and fat) tissues at 1, 2.5, and 24 h. Hyperglycemia with euinsulinemia caused a two- to threefold increase in brain GLUT-3, liver GLUT-1, and myocardial GLUT-1 concentrations only at 1 h. There was no change in GLUT-4 protein amounts at any time during the selective hyperglycemia. In contrast, selective hyperinsulinemia with euglycemia led to an immediate and persistent twofold increase in liver GLUT-1, which lasted from 1 until 24 h with a concomitant decline in myocardial tissue GLUT-4 amounts, reaching statistical significance at 24   h. No other significant change in response to hyperinsulinemia was noted in any of the other isoforms in any of the other tissues. Simultaneous assessment of total fetal glucose utilization rate (GUR f ) during selective hyperglycemia demonstrated a transient 40% increase at 1 and 2.5 h, corresponding temporally with a transient increase in brain GLUT-3 and liver and myocardial GLUT-1 protein amounts. In contrast, selective hyperinsulinemia led to a sustained increase in GUR f , corresponding temporally with the persistent increase in hepatic GLUT-1 concentrations. We conclude that excess substrate acutely increases GUR f associated with an increase in various tissues of the transporter isoforms GLUT-1 and GLUT-3 that mediate fetal basal glucose transport without an effect on the GLUT-4 isoform that mediates insulin action. This contrasts with the tissue-specific effects of selective hyperinsulinemia with a sustained increase in GUR f associated with a sustained increase in hepatic basal glucose transporter (GLUT-1) amounts and a myocardial-specific emergence of mild insulin resistance associated with a downregulation of GLUT-4. development; brain; myocardium; adipose tissue; liver