Summary
The genetically obese Zucker rat (fa/fa) is an animal model with severe insulin resistance of the skeletal muscle. We investigated whether a defect of insulin-dependent glucose transporter (GLUT 4) translocation might contribute to the pathogenesis of the insulin-resistant state. fa/fa rats, lean controls (Fa/Fa) as well as normal Wistar rats were injected intraperitoneally with insulin and were killed after 2 or 20 min, respectively. Subcellular fractions were prepared from-hind-limb skeletal muscle and were characterized by determination of marker-enzyme activities and immunoblotting applying antibodies against α1 Na+/K+ AT Pase. The relative amounts of GLUT 1 and GLUT 4 were determined in the fractions by immunoblotting with the respective antibodies. Insulin induced an approximately two-fold increase of GLUT 4 in a plasma membrane and transverse tubule enriched fraction and a decrease in the low density enriched membrane fraction in all three groups of rats. There was a high individual variation in GLUT 4 translocation efficiency within the groups. However, no statistically significant difference was noted between the groups. No effect of insulin was detectable on the distribution of GLUT 1 or α1 Na+K+ ATPase. The data suggest that skeletal muscle insulin resistance of obese Zucker rats is not associated with a lack of GLUT 4 translocation.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Bray CA (1977) The Zucker-fatty rat: a review. Fed Proc 36: 148–153
Crettaz M, Prentki M, Zaninetti D, Jeanrenaud B (1980) Insulin resistance in soleus muscle from obese Zucker rats. Biochem J 186: 525–534
Crettaz M, Zaninetti D, Jeanrenaud B (1981) Insulin resistance in heart and skeletal muscles of genetically obese Zucker rats. Biochem Soc Trans 9: 524–525
Czech MP, Richardson DK, Becker SG, Walters CG, Gitomer W, Heinrich J (1978) Insulin response in skeletal muscle and fat cells of the genetically obese Zucker rat. Metab Clin Exp 27 [Suppl 2]: 1967–1981
Kemmer FW, Berger M, Herberg L, Gries FA, Wirdeier A, Becker K (1979) Glucose metabolism in perfused skeletal muscle: demonstration of insulin resistance in obese Zucker rat. Biochem J 178: 733–741
Ferrannini E, Haffner SM, Mitchell BD, Stern MP (1991) Hyperinsulinaemia: the key feature of a cardiovascular and metabolic syndrome. Diabetologia 34: 416–422
Warram JH, Martin BH, Krolewski AS, Soeldner JS, Kahn CR (1990) Slow glucose removal rate and hyperinsulinemia precede the development of type 2 diabetes in the offspring of diabetic patients. Ann Intern Med 113: 909–915
Eriksson J, Franssila-Kallunki A, Ekstrand A et al. (1989) Early metabolic defects in persons at increased risk for non-insulin-dependent diabetes mellitus. N Engl J Med 321: 337–343
Sherman WM, Katz AL, Cutler CL, Withers RT, Ivy JI (1988) Glucose transport: locus of muscle insulin resistance in obese Zucker rats. Am J Physiol 255: E374-E382
Kahn BB, Charrou MJ, Lodish MF, Cushman SW, Flier FS (1989) Differential regulation of two glucose transporters in adipose cells from diabetic and insulin-treated diabetic rats. J Clin Invest 84: 404–411
King PA, Horton ED, Hirshman MF, Horton ES (1992) Insulin resistance in obese Zucker rat (fa/fa), skeletal muscle is associated with a failure of glucose transporter translocation. J Clin Invest 90: 1568–1575
Kahn BB, Rosetti L, Lodish HF, Charon MJ (1991) Decreased in vivo glucose uptake but normal expression of GLUT 1 and GLUT 4 in skeletal muscle of diabetic rats. J Clin Invest 87: 2197–2206
Kahn BB (1992) Facilitative glucose transporters: regulatory mechanism and dysregulation in diabetes. J Clin Invest 89: 1367–1374
Häring H, Obermaier-Kusser B (1989) Insulin receptor kinase defects in insulin-resistant tissues and their role in the pathogenesis of NIDDM. Diabetes/Metabolism Reviews 5: 431–441
Slieker LJ, Roberts EF, Shaw WW, Johnson WT (1990) Effect of streptozotocin-induced diabetes on insulin-receptor tyrosine kinase activity in obese Zucker rats. Diabetes 39: 619–625
Burdett E, Beeler T, Klip A (1987) Distribution of glucose transporters and insulin receptors in the plasma membrane and transverse tubules of skeletal muscle. Arch Biochem Biophys 253: 279–286
Simpson IA, Cushman SW (1986) Hormonal regulation of mammalian glucose transport. Annu Rev Biochem 55: 1059–1089
Pedersen O, Kahn R, Kahn BB (1992) Divergent regulation of the GLUT 1 and GLUT 4 glucose transporters in isolated adipocytes from Zucker rats. J Clin Invest 89: 1964–1973
Klip A, Pâquet M (1990) Glucose transport and glucose transporters in muscle and their metabolic regulation. Diabetes Care 13: 228–243
Obermaier-Kusser B, Mühlbacher CH, Rattenhuber E et al. (1988) Further evidence for a two step model of glucose transport regulation. Biochem J 261: 699–705
Klip A, Ramlal T, Bilan PJ, Carter GD (1990) Recruitment of GLUT 4 glucose transporters by insulin in diabetic rat skeletal muscle. Biochem Biophys Res Commun 172: 728–736
Klip A, Ramlal T, Young DA, Hooloszy JO (1987) Insulin-induced translocation of glucose transporters in rat hindlimb muscle. FEBS letters 224: 224
Hidalgo C, Gonzales ME, Lagos R (1983) Characterization of the Ca- or Mg-ATPase of transverse tubule membranes isolated from rabbit skeletal muscle. J Biol Chem 258: 13937–13945
Schimmel SD, Kent C, Bischoff R, Vagelos R (1973) Plasma membranes from cultured muscle cells: isolation procedure and separation of putative plasma-membrane marker enzymes. Proc Natl Acad Sci USA 70: 3195–3199
Douen AG, Burdett E, Ramlal T, Rastogi S, Vranic M, Klip A (1991) Characterization of glucose transporter-enriched membranes from rat skeletal muscle: assessment of endothelial cell contamination and presence of sarcoplasmic reticulum and transverse tubules. Endocrinology 128: 611–616
Marette A, Burdett E, Douen A, Vranic CM, Klip A (1992) Insulin induces the translocation of GLUT 4 from a unique intracellular organelle to transverse tubules in rat skeletal muscle. Diabetes 41: 1562–1569
Laemmli UK (1970) Cleavage of structural protein during the assembly of the head of bacteriophage T4. Nature (London) 227: 680–685
Bader S, Scholz R, Kellerer M et al. (1992) Normal insulin receptor tyrosine kinase activity and glucose transporter (GLUT 4) levels in the skeletal muscle of hyperinsulinaemic hypertensive rats. Diabetologia 35: 712–718
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Galante, P., Maerker, E., Scholz, R. et al. Insulin-induced translocation of GLUT 4 in skeletal muscle of insulin-resistant Zucker rats. Diabetologia 37, 3–9 (1994). https://doi.org/10.1007/BF00428770
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00428770