Abstract
The eukaryotic facilitated glucose transporter (GT) is expressed by many cell types, with the notable exception of hepatocytes; however, GT is expressed by several hepatoma cell lines, including the well-differentiated lines Fao, Hep3B, and HepG2. We report on studies carried out to determine the aspect(s) of the transformed phenotype that might be responsible for activating GT expression. Using RNA blot analysis with probes derived from rat GT cDNA, we found that GT was expressed by rat hepatocytes under two conditions (i) in vitro, when isolated hepatocytes were placed in cell culture, and (ii) in vivo, when rats were subjected to starvation for greater than or equal to 2 days. However, GT expression was not an obligatory feature of hepatomas, since two primary hepatocellular carcinomas did not express any GT mRNA. GT expression in hepatocytes was reduced by addition of dimethyl sulfoxide or sodium butyrate to the culture medium. Since these reagents are known to promote differentiation in some cell culture systems, their effect on hepatocytes may be to maintain the GT repression normally observed in vivo. Inclusion or exclusion in the culture medium of several other agents that enhance hepatocyte viability (serum, insulin, corticosteroids, epidermal growth factor, or triiodothyronine) did not affect GT expression. It is unclear whether the two conditions that led to GT expression in hepatocytes are related by a common signaling mechanism. Possibly, both cases involve a "stress" response: in vivo, a normal physiological response to starvation; in vitro, a response to a major alteration in the cellular environment.
Full text
PDF




Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Anderson J. W., Bridges S. R. Short-chain fatty acid fermentation products of plant fiber affect glucose metabolism of isolated rat hepatocytes. Proc Soc Exp Biol Med. 1984 Nov;177(2):372–376. doi: 10.3181/00379727-177-41958. [DOI] [PubMed] [Google Scholar]
- Aviv H., Leder P. Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1408–1412. doi: 10.1073/pnas.69.6.1408. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Birnbaum M. J., Haspel H. C., Rosen O. M. Cloning and characterization of a cDNA encoding the rat brain glucose-transporter protein. Proc Natl Acad Sci U S A. 1986 Aug;83(16):5784–5788. doi: 10.1073/pnas.83.16.5784. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Birnbaum M. J., Haspel H. C., Rosen O. M. Transformation of rat fibroblasts by FSV rapidly increases glucose transporter gene transcription. Science. 1987 Mar 20;235(4795):1495–1498. doi: 10.1126/science.3029870. [DOI] [PubMed] [Google Scholar]
- Bissell D. M., Arenson D. M., Maher J. J., Roll F. J. Support of cultured hepatocytes by a laminin-rich gel. Evidence for a functionally significant subendothelial matrix in normal rat liver. J Clin Invest. 1987 Mar;79(3):801–812. doi: 10.1172/JCI112887. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Boffa L. C., Vidali G., Mann R. S., Allfrey V. G. Suppression of histone deacetylation in vivo and in vitro by sodium butyrate. J Biol Chem. 1978 May 25;253(10):3364–3366. [PubMed] [Google Scholar]
- Cathala G., Savouret J. F., Mendez B., West B. L., Karin M., Martial J. A., Baxter J. D. A method for isolation of intact, translationally active ribonucleic acid. DNA. 1983;2(4):329–335. doi: 10.1089/dna.1983.2.329. [DOI] [PubMed] [Google Scholar]
- Chen C. C., Kurokawa T., Shaw S. Y., Tillotson L. G., Kalled S., Isselbacher K. J. Human erythrocyte glucose transporter: normal asymmetric orientation and function in liposomes. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2652–2656. doi: 10.1073/pnas.83.8.2652. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ciaraldi T. P., Horuk R., Matthaei S. Biochemical and functional characterization of the rat liver glucose-transport system. Comparisons with the adipocyte glucose-transport system. Biochem J. 1986 Nov 15;240(1):115–123. doi: 10.1042/bj2400115. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clayton D. F., Harrelson A. L., Darnell J. E., Jr Dependence of liver-specific transcription on tissue organization. Mol Cell Biol. 1985 Oct;5(10):2623–2632. doi: 10.1128/mcb.5.10.2623. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cushman S. W., Wardzala L. J. Potential mechanism of insulin action on glucose transport in the isolated rat adipose cell. Apparent translocation of intracellular transport systems to the plasma membrane. J Biol Chem. 1980 May 25;255(10):4758–4762. [PubMed] [Google Scholar]
- D'Amore T., Lo T. C. Hexose transport in L6 rat myoblasts. I. Rate-limiting step, kinetic properties, and evidence for two systems. J Cell Physiol. 1986 Apr;127(1):95–105. doi: 10.1002/jcp.1041270113. [DOI] [PubMed] [Google Scholar]
- Flier J. S., Mueckler M. M., Usher P., Lodish H. F. Elevated levels of glucose transport and transporter messenger RNA are induced by ras or src oncogenes. Science. 1987 Mar 20;235(4795):1492–1495. doi: 10.1126/science.3103217. [DOI] [PubMed] [Google Scholar]
- Flier J. S., Mueckler M., McCall A. L., Lodish H. F. Distribution of glucose transporter messenger RNA transcripts in tissues of rat and man. J Clin Invest. 1987 Feb;79(2):657–661. doi: 10.1172/JCI112864. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gattoni-Celli S., Kirsch K., Kalled S., Isselbacher K. J. Expression of type C-related endogenous retroviral sequences in human colon tumors and colon cancer cell lines. Proc Natl Acad Sci U S A. 1986 Aug;83(16):6127–6131. doi: 10.1073/pnas.83.16.6127. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Giguere V., Ong E. S., Segui P., Evans R. M. Identification of a receptor for the morphogen retinoic acid. Nature. 1987 Dec 17;330(6149):624–629. doi: 10.1038/330624a0. [DOI] [PubMed] [Google Scholar]
- Haspel H. C., Wilk E. W., Birnbaum M. J., Cushman S. W., Rosen O. M. Glucose deprivation and hexose transporter polypeptides of murine fibroblasts. J Biol Chem. 1986 May 25;261(15):6778–6789. [PubMed] [Google Scholar]
- James D. E., Brown R., Navarro J., Pilch P. F. Insulin-regulatable tissues express a unique insulin-sensitive glucose transport protein. Nature. 1988 May 12;333(6169):183–185. doi: 10.1038/333183a0. [DOI] [PubMed] [Google Scholar]
- Kasahara M., Inui K., Takano M., Hori R. Distinction of three types of D-glucose transport systems in animal cells. Biochem Biophys Res Commun. 1985 Oct 30;132(2):490–496. doi: 10.1016/0006-291x(85)91160-x. [DOI] [PubMed] [Google Scholar]
- Kioussis D., Eiferman F., van de Rijn P., Gorin M. B., Ingram R. S., Tilghman S. M. The evolution of alpha-fetoprotein and albumin. II. The structures of the alpha-fetoprotein and albumin genes in the mouse. J Biol Chem. 1981 Feb 25;256(4):1960–1967. [PubMed] [Google Scholar]
- Klip A., Walker D., Ransome K. J., Schroer D. W., Lienhard G. E. Identification of the glucose transporter in rat skeletal muscle. Arch Biochem Biophys. 1983 Oct 1;226(1):198–205. doi: 10.1016/0003-9861(83)90285-0. [DOI] [PubMed] [Google Scholar]
- Klip A., Walker D., Ransome K. J., Schroer D. W., Lienhard G. E. Identification of the glucose transporter in rat skeletal muscle. Arch Biochem Biophys. 1983 Oct 1;226(1):198–205. doi: 10.1016/0003-9861(83)90285-0. [DOI] [PubMed] [Google Scholar]
- Lienhard G. E., Kim H. H., Ransome K. J., Gorga J. C. Immunological identification of an insulin-responsive glucose transporter. Biochem Biophys Res Commun. 1982 Apr 14;105(3):1150–1156. doi: 10.1016/0006-291x(82)91090-7. [DOI] [PubMed] [Google Scholar]
- Melton D. A., Krieg P. A., Rebagliati M. R., Maniatis T., Zinn K., Green M. R. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984 Sep 25;12(18):7035–7056. doi: 10.1093/nar/12.18.7035. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mueckler M., Caruso C., Baldwin S. A., Panico M., Blench I., Morris H. R., Allard W. J., Lienhard G. E., Lodish H. F. Sequence and structure of a human glucose transporter. Science. 1985 Sep 6;229(4717):941–945. doi: 10.1126/science.3839598. [DOI] [PubMed] [Google Scholar]
- Scher W., Waxman S. Effects of dexamethasone and phorbol myristate acetate on the induction of differentiation in mouse erythroleukemic cells by dimethyl sulfoxide, proteases, and other compounds. Ann N Y Acad Sci. 1983;411:180–190. doi: 10.1111/j.1749-6632.1983.tb47300.x. [DOI] [PubMed] [Google Scholar]
- Shows T. B., Eddy R. L., Byers M. G., Fukushima Y., Dehaven C. R., Murray J. C., Bell G. I. Polymorphic human glucose transporter gene (GLUT) is on chromosome 1p31.3----p35. Diabetes. 1987 Apr;36(4):546–549. doi: 10.2337/diab.36.4.546. [DOI] [PubMed] [Google Scholar]
- Shubeita H. E., Sambrook J. F., McCormick A. M. Molecular cloning and analysis of functional cDNA and genomic clones encoding bovine cellular retinoic acid-binding protein. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5645–5649. doi: 10.1073/pnas.84.16.5645. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Suzuki K., Kono T. Evidence that insulin causes translocation of glucose transport activity to the plasma membrane from an intracellular storage site. Proc Natl Acad Sci U S A. 1980 May;77(5):2542–2545. doi: 10.1073/pnas.77.5.2542. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wang C. The D-glucose transporter is tissue-specific. Skeletal muscle and adipose tissue have a unique form of glucose transporter. J Biol Chem. 1987 Nov 15;262(32):15689–15695. [PubMed] [Google Scholar]
- Wheeler T. J., Hinkle P. C. The glucose transporter of mammalian cells. Annu Rev Physiol. 1985;47:503–517. doi: 10.1146/annurev.ph.47.030185.002443. [DOI] [PubMed] [Google Scholar]
- Wheeler T. J., Simpson I. A., Sogin D. C., Hinkle P. C., Cushman S. W. Detection of the rat adipose cell glucose transporter with antibody against the human red cell glucose transporter. Biochem Biophys Res Commun. 1982 Mar 15;105(1):89–95. doi: 10.1016/s0006-291x(82)80014-4. [DOI] [PubMed] [Google Scholar]
- Witters L. A., Alberico L., Avruch J. Insulin regulation of glycogen synthase in the isolated rat hepatocyte. Biochem Biophys Res Commun. 1976 Apr 19;69(4):997–1003. doi: 10.1016/0006-291x(76)90471-x. [DOI] [PubMed] [Google Scholar]
- Yamada K., Tillotson L. G., Isselbacher K. J. Regulation of hexose carriers in chicken embryo fibroblasts. Effect of glucose starvation and role of protein synthesis. J Biol Chem. 1983 Aug 25;258(16):9786–9792. [PubMed] [Google Scholar]









