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The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1990 Mar;85(3):962–967. doi: 10.1172/JCI114526

Glucose transporter levels in spontaneously obese (db/db) insulin-resistant mice.

L Koranyi 1, D James 1, M Mueckler 1, M A Permutt 1
PMCID: PMC296517  PMID: 2312736

Abstract

In the present study we examined mRNA and protein levels for the muscle/adipose tissue glucose transporter (GLUT-4) in various tissues of spontaneously obese mice (C57BL/KsJ, db/db) and their lean littermates (db/+). Obese (db/db) mice were studied at 5 wk of age, when they were rapidly gaining weight and were severely insulin resistant, evidenced by hyperglycemia (plasma glucose 683 +/- 60 vs. 169 +/- 4 mg/dl in db/+, P less than 0.05) and hyperinsulinemia (plasma insulin 14.9 +/- 0.53 vs. 1.52 +/- 0.08 ng/ml in db/+, P less than 0.05). The GLUT-4 mRNA was reduced in quadriceps muscle (67.5 +/- 8.5%, P = 0.02), but unaltered in adipose tissue (120 +/- 19%, NS), heart (95.7 +/- 6.1%, NS), or diaphragm (75.2 +/- 12.1%, NS) in obese (db/db) mice relative to levels in lean littermates. The GLUT-4 protein, measured by quantitative immunoblot analysis using two different GLUT-4 specific antibodies, was not different in five insulin-sensitive tissues including diaphragm, heart, red and white quadriceps muscle, and adipose tissue of obese (db/db) mice compared with tissue levels in lean littermates; these findings were consistent when measured relative to tissue DNA levels as an index of cell number. These data suggest that the marked defect in glucose utilization previously described in skeletal muscle of these young obese mice is not due to a decrease in the level of the major muscle glucose transporter. An alternate step in insulin-dependent activation of the glucose transport process is probably involved.

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Selected References

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  1. BUSE M. G., BUSE J. The effect of denervation and insulin on the penetration of D-xylose into rat hemidiaphragms. Diabetes. 1961 Mar-Apr;10:134–141. doi: 10.2337/diab.10.2.134. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Birnbaum M. J. Identification of a novel gene encoding an insulin-responsive glucose transporter protein. Cell. 1989 Apr 21;57(2):305–315. doi: 10.1016/0092-8674(89)90968-9. [DOI] [PubMed] [Google Scholar]
  4. Björntorp P., Berchtold P., Holm J., Larsson B. The glucose uptake of human adipose tissue in obesity. Eur J Clin Invest. 1971 Sep;1(6):480–485. doi: 10.1111/j.1365-2362.1971.tb00559.x. [DOI] [PubMed] [Google Scholar]
  5. Chan T. M., Dehaye J. P. Hormone regulation of glucose metabolism in the genetically obese-diabetic mouse (db/db): glucose metabolism in the perfused hindquarters of lean and obese mice. Diabetes. 1981 Mar;30(3):211–218. doi: 10.2337/diab.30.3.211. [DOI] [PubMed] [Google Scholar]
  6. Chan T. M., Tatoyan A. Glucose transport and metabolism in the perfused hindquarters of lean and obese-hyperglycemic (db/db) mice. Effects of insulin and electrical stimulation. Biochim Biophys Acta. 1984 Apr 24;798(3):325–332. doi: 10.1016/0304-4165(84)90106-5. [DOI] [PubMed] [Google Scholar]
  7. Charron M. J., Brosius F. C., 3rd, Alper S. L., Lodish H. F. A glucose transport protein expressed predominately in insulin-responsive tissues. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2535–2539. doi: 10.1073/pnas.86.8.2535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  9. Coleman D. L. Obese and diabetes: two mutant genes causing diabetes-obesity syndromes in mice. Diabetologia. 1978 Mar;14(3):141–148. doi: 10.1007/BF00429772. [DOI] [PubMed] [Google Scholar]
  10. Cuendet G. S., Loten E. G., Jeanrenaud B., Renold A. E. Decreased basal, noninsulin-stimulated glucose uptake and metabolism by skeletal soleus muscle isolated from obese-hyperglycemic (ob/ob) mice. J Clin Invest. 1976 Nov;58(5):1078–1088. doi: 10.1172/JCI108559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. DeFronzo R. A. Lilly lecture 1987. The triumvirate: beta-cell, muscle, liver. A collusion responsible for NIDDM. Diabetes. 1988 Jun;37(6):667–687. doi: 10.2337/diab.37.6.667. [DOI] [PubMed] [Google Scholar]
  12. Eriksson J., Franssila-Kallunki A., Ekstrand A., Saloranta C., Widén E., Schalin C., Groop L. Early metabolic defects in persons at increased risk for non-insulin-dependent diabetes mellitus. N Engl J Med. 1989 Aug 10;321(6):337–343. doi: 10.1056/NEJM198908103210601. [DOI] [PubMed] [Google Scholar]
  13. Fukumoto H., Kayano T., Buse J. B., Edwards Y., Pilch P. F., Bell G. I., Seino S. Cloning and characterization of the major insulin-responsive glucose transporter expressed in human skeletal muscle and other insulin-responsive tissues. J Biol Chem. 1989 May 15;264(14):7776–7779. [PubMed] [Google Scholar]
  14. Fukumoto H., Seino S., Imura H., Seino Y., Eddy R. L., Fukushima Y., Byers M. G., Shows T. B., Bell G. I. Sequence, tissue distribution, and chromosomal localization of mRNA encoding a human glucose transporter-like protein. Proc Natl Acad Sci U S A. 1988 Aug;85(15):5434–5438. doi: 10.1073/pnas.85.15.5434. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Garvey W. T., Huecksteadt T. P., Birnbaum M. J. Pretranslational suppression of an insulin-responsive glucose transporter in rats with diabetes mellitus. Science. 1989 Jul 7;245(4913):60–63. doi: 10.1126/science.2662408. [DOI] [PubMed] [Google Scholar]
  16. Garvey W. T., Huecksteadt T. P., Matthaei S., Olefsky J. M. Role of glucose transporters in the cellular insulin resistance of type II non-insulin-dependent diabetes mellitus. J Clin Invest. 1988 May;81(5):1528–1536. doi: 10.1172/JCI113485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. James D. E., Burleigh K. M., Kraegen E. W. Time dependence of insulin action in muscle and adipose tissue in the rat in vivo. An increasing response in adipose tissue with time. Diabetes. 1985 Oct;34(10):1049–1054. doi: 10.2337/diab.34.10.1049. [DOI] [PubMed] [Google Scholar]
  19. James D. E., Strube M., Mueckler M. Molecular cloning and characterization of an insulin-regulatable glucose transporter. Nature. 1989 Mar 2;338(6210):83–87. doi: 10.1038/338083a0. [DOI] [PubMed] [Google Scholar]
  20. Kahn B. B., Charron M. J., Lodish H. F., Cushman S. W., Flier J. S. Differential regulation of two glucose transporters in adipose cells from diabetic and insulin-treated diabetic rats. J Clin Invest. 1989 Aug;84(2):404–411. doi: 10.1172/JCI114180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kaku K., Province M., Permutt M. A. Genetic analysis of obesity-induced diabetes associated with a limited capacity to synthesize insulin in C57BL/KS mice: evidence for polygenic control. Diabetologia. 1989 Sep;32(9):636–643. doi: 10.1007/BF00274249. [DOI] [PubMed] [Google Scholar]
  22. Koranyi L., Permutt M. A., Chirgwin J. M., Giddings S. J. Proinsulin I and II gene expression in inbred mouse strains. Mol Endocrinol. 1989 Nov;3(11):1895–1902. doi: 10.1210/mend-3-11-1895. [DOI] [PubMed] [Google Scholar]
  23. Labarca C., Paigen K. A simple, rapid, and sensitive DNA assay procedure. Anal Biochem. 1980 Mar 1;102(2):344–352. doi: 10.1016/0003-2697(80)90165-7. [DOI] [PubMed] [Google Scholar]
  24. MORGAN H. E., CADENAS E., REGEN D. M., PARK C. R. Regulation of glucose uptake in muscle. II. Rate-limiting steps and effects of insulin and anoxia in heart muscle from diabetic rats. J Biol Chem. 1961 Feb;236:262–268. [PubMed] [Google Scholar]
  25. 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]
  26. Orland M. J., Permutt M. A. Quantitative analysis of pancreatic proinsulin mRNA in genetically diabetic (db/db) mice. Diabetes. 1987 Mar;36(3):341–347. doi: 10.2337/diab.36.3.341. [DOI] [PubMed] [Google Scholar]
  27. Simpson I. A., Cushman S. W. Hormonal regulation of mammalian glucose transport. Annu Rev Biochem. 1986;55:1059–1089. doi: 10.1146/annurev.bi.55.070186.005211. [DOI] [PubMed] [Google Scholar]
  28. Sivitz W. I., DeSautel S. L., Kayano T., Bell G. I., Pessin J. E. Regulation of glucose transporter messenger RNA in insulin-deficient states. Nature. 1989 Jul 6;340(6228):72–74. doi: 10.1038/340072a0. [DOI] [PubMed] [Google Scholar]
  29. Stauffacher W., Renold A. E. Effect of insulin in vivo on diaphragm and adipose tissue of obese mice. Am J Physiol. 1969 Jan;216(1):98–105. doi: 10.1152/ajplegacy.1969.216.1.98. [DOI] [PubMed] [Google Scholar]
  30. Thorens B., Sarkar H. K., Kaback H. R., Lodish H. F. Cloning and functional expression in bacteria of a novel glucose transporter present in liver, intestine, kidney, and beta-pancreatic islet cells. Cell. 1988 Oct 21;55(2):281–290. doi: 10.1016/0092-8674(88)90051-7. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. Young D. A., Uhl J. J., Cartee G. D., Holloszy J. O. Activation of glucose transport in muscle by prolonged exposure to insulin. Effects of glucose and insulin concentrations. J Biol Chem. 1986 Dec 5;261(34):16049–16053. [PubMed] [Google Scholar]
  33. Ziel F. H., Venkatesan N., Davidson M. B. Glucose transport is rate limiting for skeletal muscle glucose metabolism in normal and STZ-induced diabetic rats. Diabetes. 1988 Jul;37(7):885–890. doi: 10.2337/diab.37.7.885. [DOI] [PubMed] [Google Scholar]

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