Abstract
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 ≈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≈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.
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Abbreviations
- IUGR:
-
intrauterine growth restriction
- GST:
-
glutathione S-transferase
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Acknowledgements
The authors thank Dr. Mike Mueckler(Washington University, St. Louis, MO) for the Glut 1 antibody, and Dr. David James (formerly at Washington University, St. Louis, MO, now at the University of Queensland, Australia) for the rabbit anti-GST rat Glut 2 fusion protein antibody that was used in some of the experiments, whereas the commercially purchased anti-GST-Glut 2 antibody was used in others. We acknowledge Dr. Mark Magnusson (Vanderbilt University, Nashville, TN) for the sheep anti-GST rat glucokinase antibody and Dr. Kasim Mookhtiar (Bristol-Myers Squibb, PRI, Princeton, NJ) for the rabbit anti-human glucokinase antibody, both of which were used in the present studies.
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Supported by the Fleur-de-Lis Funds, St. Louis, MO (H.F.S.), American Diabetes Association (S.U.D.), and National Institutes of Health Grants HD25024 (S.U.D.), HD33997 (S.U.D.), and HL55600 (D.E.d).
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Sadiq, H., Demello, D. & Devaskar, S. The Effect of Intrauterine Growth Restriction upon Fetal and Postnatal Hepatic Glucose Transporter and Glucokinase Proteins. Pediatr Res 43, 91–100 (1998). https://doi.org/10.1203/00006450-199801000-00014
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DOI: https://doi.org/10.1203/00006450-199801000-00014
