The effect of intrauterine growth restriction upon fetal and postnatal hepatic glucose transporter and glucokinase proteins.
Employing immunohistochemical and Western blot analyses, we investigated the cellular localization (22-d fetal and 14-d postnatal animals) and concentrations (22-d fetal to 21-d postnatal animals) of rat hepatic glucose transporters (Glut 1 and Glut 2) and glucokinase in response to development and uteroplacental insufficiency with IUGR. Glut 1, the predominant fetal hematopoietic cellular isoform, persisted in postnatal hematopoietic islands and was noted minimally in fetal hepatic cellular membranes. A approximately 40% extrauterine decline in Glut 1 levels paralleled the decline in hematopoietic cells. IUGR increased the fetal hepatic Glut 1 levels in parallel with an expanded hematopoietic cell mass (p < 0.05). In contrast, IUGR failed to alter the 2-fold increase in extrauterine Glut 2 concentrations (1-7-d postnatal animals), the isoform found in fetal and postnatal hepatocytic cell membranes. Glucokinase, the nuclear enzyme, increased 25% postnatally. IUGR caused a 16% increase in fetal glucokinase levels and a approximately 25% decline at postnatal d 1 (p < 0.05) without a comparable change in the hepatocytic cell number (92 +/- 6 versus 86 +/- 4). We conclude that hepatic Glut 1 concentrations reflect the extramedullary hematopoietic cellular mass, whereas extrauterine Glut 2 changes herald the need for enhanced flexibility in hepatocytic glucose transport with the initiation of food ingestion. The age-related alteration along with the IUGR-induced compensatory changes in the nuclear-mitochondrial glucokinase levels attributes a critical role for this enzyme in perinatal hepatocytic glucose homeostasis.
Sadiq
H F
HF
Department of Pediatrics, St. Louis Health Sciences Center, Cardinal Glennon Children's Hospital, Missouri 63104, USA.
deMello
D E
DE
Devaskar
S U
SU
D000818:Animals; D005314:Embryonic and Fetal Development; D005260:Female; D005317:Fetal Growth Retardation; D005941:Glucokinase / Q000502:physiology*; D051272:Glucose Transporter Type 1; D051273:Glucose Transporter Type 2; D007150:Immunohistochemistry; D009004:Monosaccharide Transport Proteins / Q000502:physiology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D051272:Glucose Transporter Type 1; D051273:Glucose Transporter Type 2; D009004:Monosaccharide Transport Proteins; C495679:Slc2a1 protein, rat; D005941:Glucokinase